Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins.

Massive GGGGCC repeat expansion in the first intron of the gene C9orf72 is the most common known cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Despite its intronic localization and lack of an ATG start codon, the repeat region is translated in all three reading frames into aggregating dipeptide-repeat (DPR) proteins, poly-(Gly-Ala), poly-(Gly-Pro) and poly-(Gly-Arg). We took an antibody-based approach to further validate the translation of DPR proteins.

Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia.

Homozygous mutations in exon 2 of TREM2, a gene involved in Nasu-Hakola disease, can cause frontotemporal dementia (FTD). Moreover, a rare TREM2 exon 2 variant (p.R47H) was reported to increase the risk of Alzheimer's disease (AD) with an odds ratio as strong as that for APOEε4.

Uncommon testicular metastasis of a primary neuroendocrine tumour of the lung.

A 52-year-old male presented with an asymptomatic palpable mass of the right testicle. Ultrasound confirmed the presence of a testicular tumour and a hemicastration was performed. None of the testis cancer-related tumour markers were elevated and histological findings revealed a neuroendocrine carcinoma, possibly a metastasis from another primary site.

Protease-activated receptor-2 deficient mice have reduced house dust mite-evoked allergic lung inflammation.

Protease-activated receptor-2 (PAR2) is abundantly expressed in the pulmonary compartment. House dust mite (HDM) is a common cause of allergic asthma and contains multiple PAR2 agonistic proteases. The aim of this study was to determine the role of PAR2 in HDM-induced allergic lung inflammation.

[Severe bronchial asthma].

The term 'difficult-to-treat asthma' indicates that the asthma is not sufficiently controlled despite prescription of high doses of asthma medication. The term 'severe asthma' is used when the asthma is still insufficiently controlled after exclusion or treatment of any complicating factors; an important complicating factor is poor compliance. Recent studies have focused on the heterogeneous character of asthma and on the definition of specific phenotypes, with the aim of developing phenotype-specific treatments.

Systemic tryptophan and kynurenine catabolite levels relate to severity of rhinovirus-induced asthma exacerbation: a prospective study with a parallel-group design.

Background: Patients with allergic asthma have exacerbations which are frequently caused by rhinovirus infection. The antiviral tryptophan-catabolising enzyme indoleamine 2,3-dioxygenase (IDO) is induced by interferon-γ and suppressed by Th2 mediators interleukin (IL)-4 and IL-13. We hypothesised that local IDO activity after viral airway infection is lower in patients with allergic asthma than in healthy controls.

Current insights into the C9orf72 repeat expansion diseases of the FTLD/ALS spectrum.

An expanded G4C2 hexanucleotide repeat in the proximal regulatory region of C9orf72 is a frequent cause of neurodegenerative diseases in the frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND) spectrum. Although primarily characterized by variably abundant pathological inclusions of TDP-43 protein, the lesion load was extended to TDP-43-negative, p62-positive neuronal and glial inclusions in extended regions of the central nervous system (CNS), particularly in cerebellum, where they may be characteristic of a C9orf72 repeat expansion. Disease mechanisms associated with repeat expansion disorders, including haploinsufficiency, RNA toxicity, and abnormal translation of expanded repeat sequences, are beginning to emerge.

Re-irradiation and hyperthermia after surgery for recurrent breast cancer.

Purpose: Evaluation of efficacy and side effects of combined re-irradiation and hyperthermia electively or for subclinical disease in the management of locoregional recurrent breast cancer.

Methods And Materials: Records of 198 patients with recurrent breast cancer treated with re-irradiation and hyperthermia from 1993 to 2010 were reviewed. Prior treatments included surgery (100%), radiotherapy (100%), chemotherapy (42%), and hormonal therapy (57%).

Europe's strong primary care systems are linked to better population health but also to higher health spending.

Strong primary care systems are often viewed as the bedrock of health care systems that provide high-quality care, but the evidence supporting this view is somewhat limited. We analyzed comparative primary care data collected in 2009-10 as part of a European Union-funded project, the Primary Health Care Activity Monitor for Europe. Our analysis showed that strong primary care was associated with better population health; lower rates of unnecessary hospitalizations; and relatively lower socioeconomic inequality, as measured by an indicator linking education levels to self-rated health.

Effect of a combined surgery, re-irradiation and hyperthermia therapy on local control rate in radio-induced angiosarcoma of the chest wall.

Purpose: Radiation-induced angiosarcoma (RAS) of the chest wall/breast has a poor prognosis due to the high percentage of local failures. The efficacy and side effects of re-irradiation plus hyperthermia (reRT + HT) treatment alone or in combination with surgery were assessed in RAS patients.

Patients And Methods: RAS was diagnosed in 23 breast cancer patients and 1 patient with melanoma.

Loss of ALS-associated TDP-43 in zebrafish causes muscle degeneration, vascular dysfunction, and reduced motor neuron axon outgrowth.

Mutations in the Tar DNA binding protein of 43 kDa (TDP-43; TARDBP) are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43(+) inclusions (FTLD-TDP). To determine the physiological function of TDP-43, we knocked out zebrafish Tardbp and its paralogue Tardbp (TAR DNA binding protein-like), which lacks the glycine-rich domain where ALS- and FTLD-TDP-associated mutations cluster. tardbp mutants show no phenotype, a result of compensation by a unique splice variant of tardbpl that additionally contains a C-terminal elongation highly homologous to the glycine-rich domain of tardbp.

C9orf72 G4C2 repeat expansions in Alzheimer's disease and mild cognitive impairment.

C9orf72 G4C2 repeat expansion is a major cause of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Its role in Alzheimer's disease (AD) is less clear. We assessed the prevalence of G4C2 pathogenic repeat expansions in Flanders-Belgian patients with clinical AD or mild cognitive impairment (MCI).

Distinct clinical characteristics of C9orf72 expansion carriers compared with GRN, MAPT, and nonmutation carriers in a Flanders-Belgian FTLD cohort.

Objective: To characterize patients with frontotemporal lobar degeneration (FTLD) with a repeat expansion mutation in the gene C9orf72, and to determine whether there are differences in the clinical presentation compared with FTLD carriers of a mutation in GRN or MAPT or with patients with FTLD without mutation.

Design: Patient series.

Setting: Dementia clinics in Flanders, Belgium.

Explorative genetic study of UBQLN2 and PFN1 in an extended Flanders-Belgian cohort of frontotemporal lobar degeneration patients.

UBQLN2 and PFN1 were recently associated with amyotrophic lateral sclerosis (ALS). We investigated a role for these ALS genes in frontotemporal lobar degeneration (FTLD). We screened 328 FTLD, 17 FTLD-ALS, and 157 ALS patients.

Description of three new species of Hylopanchax Poll & Lambert, 1965 from the central Congo Basin (Cyprinodontiformes: Poeciliidae: Procatopodini) with a redefinition of the genus.

Three new species of the lampeye genus Hylopanchax are described from the central Congo basin: H. leki, new species, H. ndeko, new species, and H.

Lipopolysaccharide inhibits Th2 lung inflammation induced by house dust mite allergens in mice.

The complex biology of asthma compels the use of more relevant human allergens, such as house dust mite (HDM), to improve the translation of animal models into human asthma. LPS exposure is associated with aggravations of asthma, but the mechanisms remain unclear. Here, we studied the effects of increasing LPS doses on HDM-evoked allergic lung inflammation.

High SNP density in the blacklegged tick, Ixodes scapularis, the principal vector of Lyme disease spirochetes.

Single-nucleotide polymorphisms (SNPs) are the most widespread type of sequence variation in genomes. SNP density and distribution varies among different organisms and genes. Here, we report the first estimates of SNP distribution and density in the genome of the blacklegged tick (Ixodes scapularis), an important vector of the pathogens causing Lyme disease, human granulocytic anaplasmosis and human babesiosis in North America.

A pan-European study of the C9orf72 repeat associated with FTLD: geographic prevalence, genomic instability, and intermediate repeats.

We assessed the geographical distribution of C9orf72 G(4) C(2) expansions in a pan-European frontotemporal lobar degeneration (FTLD) cohort (n = 1,205), ascertained by the European Early-Onset Dementia (EOD) consortium. Next, we performed a meta-analysis of our data and that of other European studies, together 2,668 patients from 15 Western European countries. The frequency of the C9orf72 expansions in Western Europe was 9.

Intrabronchial activated protein C enhances lipopolysaccharide-induced pulmonary responses.

Intravenous administration of activated protein C (APC) inhibits coagulation and inflammation in the lungs of humans and animals. Investigations in rodents demonstrated that direct intrapulmonary delivery of APC also exerts anticoagulant and anti-inflammatory effects. The effect of intrabronchial administration of recombinant human (rh)APC on lipopolysaccharide (LPS)-induced haemostatic and inflammatory alterations in the bronchoalveolar space of humans was studied.

A 24-year-old Ethiopian farmer with burning feet.

Podoconiosis is a non-infectious tropical disease caused by exposure of bare feet to irritant alkalic clay soils. This causes an asymmetrical swelling of the feet and lower limbs due to lymphoedema. This swelling is called "elephantiasis" and may lead to severe disability of the patient.

Gene expression profiles in alveolar macrophages induced by lipopolysaccharide in humans.

Lipopolysaccharide (LPS) is ubiquitous in the environment. Inhalation of LPS has been implicated in the pathogenesis and/or severity of several lung diseases, including pneumonia, chronic obstructive pulmonary disease and asthma. Alveolar macrophages are the main resident leukocytes exposed to inhaled antigens.

Bcl-2 associated anthanogen-1 (Bag-1) expression and prognostic value in pancreatic head and periampullary cancer.

The expression of anti-apoptosis gene Bcl-2 associated anthanogen-1 (Bag-1), has been associated with outcome in several cancer types, however its prognostic role in pancreatic cancer is unknown. Aim was therefore to evaluate expression of Bag-1 in two anatomically closely related however prognostically different tumours, pancreatic head- and periampullary cancer and correlate expression with outcome. Bag-1 protein expression was studied by immunohistochemistry on original paraffin embedded tissue from 217 patients with microscopic radical resection (R0) of adenocarcinoma of the pancreatic head or periampullary region.

Tumour basement membrane laminin expression predicts outcome following curative resection of pancreatic head cancer.

Background: Although widely fragmented BMs have been associated with adverse outcome in several cancer types, comparatively little is known with respect to its effect on the prognosis of pancreatic cancer. The aim of the current study was therefore to determine the prognostic value of tumour basement membrane (BM) continuity in two anatomically closely related, however, prognostically different tumours, pancreatic head- and periampullary cancer.

Methods: Tumour BM continuity was determined by immunohistochemical staining of its two major components, laminin and collagen type IV.