MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response

MicroRNAs (miRNAs) are small noncoding RNAs, 19-24 nucleotides in length, that regulate gene expression and are expressed aberrantly in most types of cancer. MiRNAs also have been detected in the blood of cancer patients and can serve as circulating biomarkers. It has been shown that secreted miRNAs within exosomes can be transferred from cell to cell and can regulate gene expression in the receiving cells by canonical binding to their target messenger RNAs. Here we show that tumor-secreted miR-21 and miR-29a also can function by another mechanism, by binding as ligands to receptors of the Toll-like receptor (TLR) family, murine TLR7 and human TLR8, in immune cells, triggering a TLR-mediated prometastatic inflammatory response that ultimately may lead to tumor growth and metastasis. Thus, by acting as paracrine agonists of TLRs, secreted miRNAs are key regulators of the tumor microenvironment. This mechanism of action of miRNAs is implicated in tumor-immune system communication and is important in tumor growth and spread, thus representing a possible target for cancer treatment.     

Eradication of chronic methicillin-resistant Staphylococcus aureus infection in cystic fibrosis patients. An observational prospective cohort study of 11 patients

BackgroundChronic airway infection with methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) is an increasing clinical problem, and therapeutic options are limited. Because chronic infection with MRSA can be associated with accelerated decline in lung function, eradication of MRSA is attempted in most CF centres today. The aim of this observational prospective cohort study was to determine whether it is possible to eradicate MRSA from airways of CF patients using prolonged oral antibiotic combination therapy together with topical decolonization measures.ResultsEleven CF patients, (median age: 9 years (range 1–43); median FEV₁: 91%pred (95%CI 74%–100%pred)) who were chronically infected with MRSA, were treated daily for six months with rifampicin and fusidic acid orally. This study did not include a patient control group. Two patients had to switch to an alternative schedule, using rifampicin and clindamycin, due to the resistance pattern of MRSA. Topical decolonization measures were applied to all patients and included mupirocin-containing nasal ointment in both nostrils three times daily for five days and chlorhexidine hair and body wash once daily for five days. Microbiological eradication was achieved in all patients at the end of the six-month eradication protocol, even when significant time (range 18 months to 9 years) had elapsed since initial isolation. In only one patient MRSA reappeared in the six-month follow-up period after the initial study period. Side-effects, like nausea, vomiting and diarrhoea were seen in five out of eleven patients, but did not lead to therapy cessation.ConclusionChronic MRSA infection can be eradicated from respiratory tract samples using a six month dual antibiotic regimen and topical MRSA decolonization measures.     

Are Mammographic Changes in the Tumor Bed More Pronounced After Intraoperative Radiotherapy for Breast Cancer? Subgroup Analysis from a Randomized Trial (TARGIT‐A)

Intraoperative radiotherapy (IORT) with low‐energy x‐rays is increasingly used in breast‐conserving therapy (BCT). Previous non‐randomized studies have observed mammographic changes in the tumor bed to be more pronounced after IORT. The purpose of this study was to reassess the postoperative changes in a randomized single‐center subgroup of patients from a multicenter trial (TARGIT‐A). In this subgroup (n = 48) 27 patients received BCT with IORT, 21 patients had BCT with standard whole‐breast radiotherapy serving as controls. Overall 258 postoperative mammograms (median follow‐up 4.3 years, range 3–8) were retrospectively evaluated by two radiologists in consensus focusing on changes in the tumor bed. Fat necroses showed to be significantly more frequent (56% versus 24%) and larger (8.7 versus 1.6 sq cm, median) after IORT than those in controls. Scar calcifications were also significantly more frequent after IORT (63% versus 19%). The high incidence of large fat necroses in our study confirms previous study findings. However, the overall higher incidence of calcifications in the tumor bed after IORT represents a new finding, requiring further attention.     

Processing consequences of superfluous and missing prosodic breaks in auditory sentence comprehension

This ERP study investigates whether a superfluous prosodic break (i.e., a prosodic break that does not coincide with a syntactic break) has more severe processing consequences during auditory sentence comprehension than a missing prosodic break (i.e., the absence of a prosodic break at the position of a syntactic break). Participants listened to temporarily ambiguous sentences involving a prosody–syntax match or mismatch. The disambiguation of these sentences was always lexical in nature in the present experiment. This contrasts with a related study by Pauker, Itzhak, Baum, and Steinhauer (2011), where the disambiguation was of a lexical type for missing PBs and of a prosodic type for superfluous PBs. Our results converge with those of Pauker et al. (2011): superfluous prosodic breaks lead to more severe processing problems than missing prosodic breaks. Importantly, the present results extend those of Pauker et al. (2011) showing that this holds when the disambiguation is always lexical in nature. Furthermore, our results show that the way listeners use prosody can change over the course of the experiment which bears consequences for future studies.     

Seroprevalence of anti-N-methyl-d-aspartate receptor antibodies in women with ovarian teratoma

Recently antibodies against neuronal receptors have been identified as cause of a new type of encephalitis. The anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis is the prototype of these disorders. Patients have a high incidence of teratomata. Removal of teratoma is considered the essential treatment of anti-NMDA-R encephalitis. Here, we aimed to investigate whether neurologically asymptomatic individuals suffering from ovarian teratomata may have positive anti-NMDA-R antibodies to be detected by an established assay. Over a time period of 15 months, all patients suffering from ovarian teratomata without neurological symptoms were included in this prospective study. Twenty consecutive patients were pair matched to patients with other benign ovarian disease and healthy controls. Preoperatively, patients had a gynaecological examination, transvaginal ultrasound, neurological examination and determination of anti-NMDA-R antibodies. None of the patients or controls presented with neurological symptoms. All tumours could be removed completely by laparoscopy. Anti-NMDA-R antibodies were absent in the group of patients with teratomata as well as in patients with benign ovarian tumours and healthy controls. Testing for anti-NMDA-R antibodies revealed negative findings in well-characterised patients with ovarian teratomata lacking neurological symptoms. Our data support the current clinical practice that a systematic screening for anti-NMDA-R antibodies in teratoma patients is not indicated.     

Effect of Wii-intervention on balance of children with poor motor performance

The purpose of this study was to investigate the effects of training with the Wii-balance board on balance and balance-related skills of children with poor motor performance. Twenty-nine children (23 boys, 6 girls; aged 7–12 years) participated in this study and were randomly assigned to an experimental and control group. All children scored below the 16th percentile on a standardized test of motor ability and balance skills (Movement Assessment Battery for children (M-ABC-2)). Before and after a six-week Wii-intervention (M = 8 h, 22 min, SD = 53 min), the balance skills of the experimental group and control group were measured with the M-ABC-2 and the Bruininks–Oseretsky test of motor proficiency (BOT-2). Both groups improved on all tests. The M-ABC-2 and the BOT-2 total balance-scores of the experimental group improved significantly from pre to post intervention, whereas those of the control group showed no significant progress. This resulted in significant interaction-effects, favoring the experimental children. No transfer-effects of the intervention on balance-related skills were demonstrated. Our findings showed that the Wii-balance board is an effective intervention for children with poor balance control. Further development and investigation of the intervention could be directed toward the implementation of the newly acquired balance-skills in daily life.     

Occurrence and co-localization of amyloid beta-protein and apolipoprotein E in perivascular drainage channels of wild-type and APP-transgenic mice

The deposition of the amyloid beta-protein (Abeta) is a hallmark of Alzheimer's disease (AD). One reason for Abeta-accumulation and deposition in the brain may be an altered drainage along perivascular channels. Extracellular fluid is drained from the brain towards the cervical lymph nodes via perivascular channels. The perivascular space around cerebral arteries is the morphological correlative of these drainage channels. Here, we show that Abeta is immunohistochemically detectable within the perivascular space of 25 months old wild-type and amyloid precursor protein (APP)-transgenic mice harboring the Swedish double mutation driven by a neuron specific promoter. Only small amounts of Abeta can be detected immunohistochemically in the perivascular space of wild-type mice. Cerebrovascular and parenchymal Abeta-deposits were absent. In APP-transgenic mice, large amounts of Abeta were found in the perivascular drainage channels accompanied with cerebrovascular and parenchymal Abeta-deposition. The apolipoprotein E (apoE) immunostaining within the perivascular channels did not vary between wild-type and APP-transgenic mice. Almost 100% of the area that represents the perivascular space was stained with an antibody directed against apoE. Here, Abeta co-localized with apoE indicating an involvement of apoE in the perivascular clearance of Abeta. Fibrillar congophilic amyloid was not seen in wild-type mice. In APP-transgenic animals, congophilic fibrillar amyloid material was seen in the wall of cerebral blood vessels but not in the perivascular space. In conclusion, our results suggest that non-fibrillar forms of Abeta are drained along perivascular channels and that apoE is presumably involved in this clearance mechanism. Overloading such a clearance mechanism in APP-transgenic mice appears to result in insufficient Abeta-clearance, increased Abeta-levels in the brain and the perivascular drainage channels, and finally in Abeta-deposition. In so doing, our results strengthen the hypothesis that an alteration of perivascular drainage supports Abeta-deposition and the development of AD.     

Trends der Lungenkrebsinzidenz nach histologischem Subtyp bei Männern und Frauen in Deutschland

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Beim Lungenkrebs werden verschiedene histologische Subtypen unterschieden. Im Wesentlichen sind dies das kleinzellige Karzinom,...     

The Impact of Dysphagia on Mortality of Nursing Home Residents: Results From the nutritionDay Project

Objectives

Dysphagia is a frequent finding in nursing home residents. The aim of this study is to evaluate the association of dysphagia and mortality in nursing home residents and identify further risk factors for mortality in residents with dysphagia.