Parkin deletion causes cerebral and systemic amyloidosis in human mutated tau over-expressing mice

Deposition of proteins leading to amyloid takes place in some neurodegenerative diseases such as Alzheimer's disease and Huntington's disease. Mutations of tau and parkin proteins produce neurofibrillary abnormalities without deposition of amyloid. Here we report that mature, parkin null, over-expressing human mutated tau (PK(-/-)/Tau(VLW)) mice have altered behaviour and dopamine neurotransmission, tau pathology in brain and amyloid deposition in brain and peripheral organs. PK(-/-)/Tau(VLW) mice have abnormal behaviour and severe drop out of dopamine neurons in the ventral midbrain, up to 70%, at 12 months and abundant phosphorylated tau positive neuritic plaques, neuro-fibrillary tangles, astrogliosis, microgliosis and plaques of murine beta-amyloid in the hippocampus. PK(-/-)/Tau(VLW) mice have organomegaly of the liver, spleen and kidneys. The electron microscopy of the liver confirmed the presence of a fibrillary protein deposits with amyloid characteristics. There is also accumulation of mouse tau in hepatocytes. These mice have lower levels of CHIP-HSP70, involved in the proteosomal degradation of tau, increased oxidative stress, measured as depletion of glutathione which, added to lack of parkin, could trigger tau accumulation and amyloidogenesis. This model is the first that demonstrates beta-amyloid deposits caused by over-expression of tau and without modification of the amyloid precursor protein, presenilins or secretases. PK(-/-)/Tau(VLW) mice provide a link between the two proteins more important for the pathogenesis of Alzheimer disease.     

How to deal with prognostic factors and radiotherapy results in uterine neoplasms with a sarcomatous component?

Purpose  

Uterine tumours with a sarcomatous component are rare neoplasms with a wide pathologic heterogeneity in which the stage is the main prognostic factor. These aspects and their aggressiveness make the analysis of prognostic factors and radiotherapy difficult. The aim of this study was to evaluate the prognostic factors by stages and to assess the impact of prognostic factors and the effect of radiotherapy on the outcome of the disease.     

Loco-regional control after postoperative radiotherapy for patients with regional nodal metastases from melanoma

Introduction  

The role of adjuvant radiation therapy (RT) following nodal surgery in malignant melanoma remains controversial. There are no published randomised trials comparing surgery alone to surgery with postoperative RT.     

Air Pollution and Recent Symptoms of Asthma,Allergic Rhinitis,and Atopic Eczema in Schoolchildren Aged Between 6 and 7 Years

ObjectiveThe objective of the study was to analyze the relationship between air pollutants and the prevalence of recent symptoms of asthma, allergic rhinitis, and atopic eczema in schoolchildren aged between 6 and 7 years.Patients and MethodsThe prevalence of recent (previous 12 months) symptoms of allergic diseases was obtained by means of the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC), Spain, with the participation of 7 centers (Asturias, Barcelona, Bilbao, Cartagena, La Coruña, Madrid, and Valencia) and 20 455 schoolchildren aged between 6 and 7 years, from 2002 to 2003. The pollutant detection systems of the aforementioned centers provided the mean annual concentrations of sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and total suspended particulate matter.ResultsThe annual average concentration of SO₂ showed a significant association with a higher prevalence of recent severe asthma (adjusted odds ratio [aOR] between level-1 and level-3 pollution, 1.32; 95% confidence interval [CI], 1.01–1.73), rhinitis (aOR, 1.56; 95% CI, 1.39–1.75), and rhinoconjunctivitis (aOR, 1.70; 95% CI, 1.45–2.00). The annual average concentration of CO was associated with a higher prevalence of rhinitis (aOR, 1.65; 95% CI, 1.34-2.04), rhinoconjunctivitis (aOR, 1.76; 95% CI, 1.31–2.37), and eczema (aOR, 1.55; 95% CI, 1.17–2.04). The annual average concentration for NO₂ and total suspended particulate matter showed inverse associations with the prevalence of nocturnal dry cough.ConclusionsFindings suggest that air pollutants such as SO₂ and CO increase the risk of recent symptoms of asthma and allergic rhinitis in schoolchildren aged between 6 and 7 years in Spain.     

Intake of Natural,Unprocessed Tiger Nuts (Cyperus esculentus L.) Drink Significantly Favors Intestinal Beneficial Bacteria in a Short Period of Time

Horchata is a natural drink obtained from tiger nut tubers (Cyperus esculentus L.). It has a pleasant milky aspect and nutty flavor; some health benefits have been traditionally attributed to it. This study evaluated the effects of an unprocessed horchata drink on the gut microbiota of healthy adult volunteers (n = 31) who consumed 300 mL of natural, unprocessed horchata with no added sugar daily for 3 days. Although there were no apparent microbial profile changes induced by horchata consumption in the studied population, differences could be determined when volunteers were segmented by microbial clusters. Three distinctive enterogroups were identified previous to consuming horchata, respectively characterized by the relative abundances of Blautia and Lachnospira (B1), Bacteroides (B2) and Ruminococcus and Bifidobacterium (B3). After consuming horchata, samples of all volunteers were grouped into two clusters, one enriched in Akkermansia, Christenellaceae and Clostridiales (A1) and the other with a remarkable presence of Faecalibacterium, Bifidobacterium and Lachnospira (A2). Interestingly, the impact of horchata was dependent on the previous microbiome of each individual, and its effect yielded microbial profiles associated with butyrate production, which are typical of a Mediterranean or vegetable/fiber-rich diet and could be related to the presence of high amylose starch and polyphenols.     

An improved method for lupus anticoagulant detection

The diagnosis of lupus anticoagulant (LA) becomes difficult when there is a weak titer of LA antibodies. This study demonstrates that 20 minutes' incubation increases the sensitivity of the mixing test to diagnose LA by 23% and to suspect the antibodies by 66%.     

Functional genetic diversity in the high-affinity carnitine transporter OCTN2 (SLC22A5)

Systemic carnitine deficiency (SCD) is a rare autosomal recessive disease resulting from defects in the OCTN2 (SLC22A5) gene, which encodes the high-affinity plasma membrane carnitine transporter. Although OCTN2 is fairly well studied in its relationship with SCD, little is known about the carrier frequency of disease-causing alleles of OCTN2, or of more common functional polymorphisms in this gene. To address these issues, we screened for genetic variants in the OCTN2 coding region by direct sequencing of the exons and flanking intronic region of OCTN2 in a large sample (n = 276) of ethnically diverse subjects. In addition, we established lymphoblastoid cell lines from subjects homozygous for either allele of the previously identified promoter region variant, -207G>C. We found eight amino acid sequence variants of OCTN2, of which three (Phe17Leu, Leu144Phe, and Pro549Ser) were polymorphic in at least one ethnic group. When assayed for functional activity by expression in human embryonic kidney 293 cells, using as probes both the endogenous substrate (l-carnitine) and the organic cation tetraethylammonium, three variants showed functional differences from the reference OCTN2 (Phe17Leu, Tyr449Asp, Val481Phe; p < 0.05). Further studies of the Phe17Leu polymorphism showed a reduced V(max) for l-carnitine transport to approximately 50% of the reference OCTN2. Confocal microscopy studies using an OCTN2-GFP fusion protein showed that Phe17Leu had distinct subcellular localization from the reference OCTN2, with diffuse cytoplasmic retention of Phe17Leu, in contrast to reference OCTN2, which localized specifically to the plasma membrane. Lymphoblasts from subjects homozygous for the -207G allele showed increased l-carnitine transport compared with the -207C/C homozygotes (p < 0.05). This study suggests that although loss-of-function mutations in OCTN2 are likely to be rare, common variants of OCTN2 found in healthy populations may contribute to variation in the disposition of carnitine and some clinically used drugs.