Activation of coagulation by administration of recombinant factor VIIa elicits interleukin 6 (IL-6) and IL-8 release in healthy human subjects

The activation of coagulation has been shown to contribute to proinflammatory responses in animal and in vitro experiments. Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma. This increase was absent when the subjects were pretreated with recombinant nematode anticoagulant protein c2, the inhibitor of tissue factor-factor VIIa.     

Classification,identification and subtyping of bacteria based on pyrosequencing and signature matching of 16S rDNA fragments

The rapid identification of the etiological agent of microbial infections can bring about both clinical and financial benefits. Thus, fast and generally applicable classification methods are needed that will enable us to rapidly distinguish pathogenic bacteria from commensals or saprophytic bacteria found in the same habitat. We here show that provisional classification of bacterial isolates can be performed on a large scale based on 16S rRNA sequence comparisons using Pyrosequencing, a recently described real-time DNA sequence analysis technique, and the concept of signature matching. The probes we have developed, together with the new technology, will enable early diagnosis of specific pathogens, which is critical for the rational use of antimicrobial therapy in clinical medicine.     

Comparison of the cardiac effects of the antimalarials co-artemether and halofantrine in healthy participants

Co-artemether (Coartem, Riamet) is a tablet containing 20 mg artemether and 120 mg lumefantrine for treatment of falciparum malaria. Lumefantrine has some chemical similarities to halofantrine (Halfan), an antimalarial known for QTc prolongation. Effects on the QTc interval of fed single oral doses of 500 mg halofantrine and 80/480 mg co-artemether were compared in 13 healthy males in a randomized double-blind crossover study. Electrocardiograms (ECGs) were recorded from 48 hours before dosing until 48 hours thereafter. The maximum QTc interval (QTc = QT/square root(RR)) was compared before and after treatment and between treatments, fitting a general linear model. Drug plasma concentrations were determined concomitantly. After halofantrine, all participants showed an increase in the QTc interval; the mean maximum increase was 28 ms. The length of the QTc interval was positively correlated to halofantrine exposure. The QTc interval remained unchanged after co-artemether. The difference between treatments was statistically significant. In conclusion, halofantrine caused a significant, exposure-dependent increase in the QTc interval. No such effect was seen with co-artemether.     

Tissue Inhibitor of Metalloproteinase-4 Is Elevated in Early-Stage Breast Cancers with Accelerated Progression and Poor Clinical Course

An increasing number of breast cancer patients are diagnosed with small, localized, early-stage tumors. These patients are typically thought to have a good prognosis for long-term disease-free survival, but epidemiological studies indicate that up to 30% may have a recurrence within 3 to 5 years of diagnosis. Identifying patients with a high risk of recurrence and/or progression is important because they could be more aggressively treated at diagnosis to improve their chances for disease-free survival. Recent evidence suggests that elevated levels of the matrix metalloproteinase inhibitor, tissue inhibitor of metalloproteinase (TIMP)-4, are associated with malignant progression of ductal carcinoma in situ, a precancerous lesion. To examine the association of TIMP-4 with survival outcomes, we conducted a retrospective immunohistochemical analysis of 314 cases from patients with early-stage disease, defined as tumors smaller than 2 cm and no spread to lymph nodes (tumor-node-metastasis staging: T1N0MX). We found that tumors with elevated levels of TIMP-4 were correlated with a reduced probability of long-term disease-free survival, especially in patients with estrogen receptor-negative tumors. Our findings prompt further evaluation of TIMP-4 as a simple prognostic marker that may help identify patients with early-stage breast cancer who could benefit from more aggressive treatment at diagnosis.Tissue inhibitor of metalloproteinase (TIMP)-4 is one of four members of the family of TIMPs, which modify the breakdown of extracellular matrix by the matrix metalloproteinases. Studies of the TIMPs in mammalian organisms have revealed distinctions in structure, biochemical properties, and tissue-specific expression patterns, suggesting unique roles in normal physiology.^1,2,3 Because of their key roles in cell motility and tissue organization, the interactions between TIMPs and matrix metalloproteinases have been widely studied in cancer research. Until recently, TIMPs were recognized primarily only as matrix metalloproteinase inhibitors. However, recent work has made it increasingly clear that TIMPs have non-matrix metalloproteinase-associated functions in cancer,⁴ including roles in growth promotion,^5,6,7 apoptosis,^8,9,10 and angiogenesis.^10,11 In the mammary gland, the importance of TIMPs has been demonstrated during normal physiological processes such as glandular development and involution during pregnancy.¹² Although TIMPs have been studied in breast cancer, TIMP-4 has received limited attention and there is conflicting information about its significance. In one study, human breast cancer cells engineered to ectopically express TIMP-4 displayed a reduction in growth and metastasis after implantation in mice.¹³ In contrast, another study showed that a gene therapy strategy to express TIMP-4 promoted mammary tumor formation.¹⁴ Notably, in human breast cancer, TIMP-4 has been associated with the transition of ductal carcinoma in situ into invasive, infiltrating ductal carcinoma (IDC).¹⁵ With an increasing number of patients being diagnosed with small early-stage tumors (<20 mm in diameter) and no signs of spread to lymph nodes, the majority of patients are predicted to have a favorable prognosis for long-term disease-free survival according to traditional tumor-node-metastases (TNM) staging. Nevertheless, epidemiological studies indicate that 20 to 30% of these patients will have a recurrence of their breast cancer within 3 to 5 years of diagnosis.^16,17 Markers that could identify this subgroup of patients who are at higher risk of relapse and/or malignant progression would be useful to stratify them for more aggressive treatment that might improve their chances for long-term disease-free survival. In this study, we tested the hypothesis that TIMP-4 expression correlates inversely with disease-free survival for patients with early-stage disease.     

More than medical treatment: the patient's first encounter with prehospital emergency care

A common feature of emergency care services is the short, fragmented encounters with great demands for rapid treatment and efficiency. The aim of this study was to describe and understand the patient's first encounter with prehospital emergency care as experienced by the patient and the first responders. A lifeworld perspective was used in four different traumatic situations. The data consisted of 18 unstructured interviews with patients and first responders. The phenomenological analysis showed that the concept of lifesaving means more than just upholding vital functions. The patient needs to retain his/her identity by means of a communicative contact, to be confirmed in the lived encounter and to recapitulate the elapsed time of the unexpected event in order to regain a state of equilibrium. Five constituents further described the variations of the patients' first encounter; the encounter with the helpless injured body, the confirming existential encounter, the encounter while waiting, the lived encounter and the recapitulated encounter. This finding highlights the importance of a new understanding about empowering the patient with narratives throughout the whole caring process. There are also implications for educating personnel and students in emergency care about the first encounter with the patient in emergency care where the senses, the time and the narrative are essential elements that are unique for each person.     

The HiNF-P/p220NPAT cell cycle signaling pathway controls nonhistone target genes

HiNF-P and its cofactor p220(NPAT) are principal factors regulating histone gene expression at the G(1)-S phase cell cycle transition. Here, we have investigated whether HiNF-P controls other cell cycle- and cancer-related genes. We used cDNA microarrays to monitor responsiveness of gene expression to small interfering RNA-mediated depletion of HiNF-P. Candidate HiNF-P target genes were examined for the presence of HiNF-P recognition motifs, in vitro HiNF-P binding to DNA, and in vivo association by chromatin immunoprecipitations and functional reporter gene assays. Of 177 proliferation-related genes we tested, 20 are modulated in HiNF-P-depleted cells and contain putative HiNF-P binding motifs. We validated that at least three genes (i.e., ATM, PRKDC, and CKS2) are HiNF-P dependent and provide data indicating that the DNA damage response is altered in HiNF-P-depleted cells. We conclude that, in addition to histone genes, HiNF-P also regulates expression of nonhistone targets that influence competency for cell cycle progression.     

Accuracy and Complications Using Computer‐Designed Stereolithographic Surgical Guides for Oral Rehabilitation by Means of Dental Implants: A Review of the Literature

Background: In the last decade several stereolithographic guided surgery systems were introduced to the market. In this context, scientific information regarding accuracy of implant placement and surgical and prosthodontical complications is highly relevant as it provides evidence to implement this surgical technique in a clinical setting. Purpose: To review data on accuracy and surgical and prosthodontical complications using stereolithographical surgical guides for implant rehabilitation. Material and Methods: PubMed database was searched using the following keywords: “three dimensional imaging,”“image based surgery,”“flapless guided surgery,”“customized drill guides,”“computer assisted surgery,”“surgical template,” and “stereolithography.” Only papers in English were selected. Additional references found through reading of selected papers completed the list. Results: In total 31 papers were selected. Ten reported deviations between the preoperative implant planning and the postoperative implant locations. One in vitro study reported a mean apical deviation of 1.0 mm, three ex vivo studies a mean apical deviation ranging between 0.6 and 1.2 mm. In six in vivo studies an apical deviation between 0.95 and 4.5 mm was found. Six papers reported on complications mounting to 42% of the cases when stereolithographic guided surgery was combined with immediate loading. Conclusion: Substantial deviations in three‐dimensional directions are found between virtual planning and actually obtained implant position. This finding and additionally reported postsurgical complications leads to the conclusion that care should be taken whenever applying this technique on a routine basis.     

The Informal Networks in Food Procurement by Older People—A Cross European Comparison

Healthy dietary profiles contribute to successful aging, and dietary intake is dependent upon food procurement capabilities. Both formal and informal social networks can contribute to grocery shopping capabilities and methods of food procurement. This investigation explores the role of informal networks in food procurement methods among adults aged 65 years and older, and compares differences across eight European countries. Food shopping ways (FSW), identified by quantitative analysis (cluster analysis and correspondence analysis), guided the content qualitative analysis which was carried out addressing three main research questions addressing food shopping routines, feelings of dependency and needs of informal support for shopping, and differences between past and present food shopping behaviours. Living circumstances influence food shopping habits. Informal networks differed between two groups of individuals: those living alone and those living with others. Gender differences emerged in shopping pleasure. Geographical factors were associated with preference for shopping companions, attitudes toward receiving support, and availability of a car for shopping. The importance of living circumstances (i.e., alone vs. with others) in FSW was revealed. Informal social networks may play an important role in public health and welfare policies, particularly given the increase in this demographic group. Assistance with grocery shopping and the availability of trained personnel could widen informal networks, and effective informal networks may be an important supportive service for older adults. The comparison across countries highlighted relationships between food procurement capabilities and social networks. These findings may be used to develop resources to better meet the nutritional needs of older adults.