EAST syndrome: Clinical, pathophysiological, and genetic aspects of mutations in KCNJ10

EAST syndrome is a recently described autosomal recessive disorder secondary to mutations in KCNJ10 (Kir4.1), a gene encoding a potassium channel expressed in the brain, eye, ear and kidney. This condition is characterized by 4 cardinal features; Epilepsy, Ataxia, Sensorineural deafness, and (a renal salt-wasting) Tubulopathy, hence the acronym EAST syndrome. Here we review reported clinical manifestations, in particular the neurological signs and symptoms which typically have the most impact on the quality of life of patients. In addition we review the pathophysiology and genetic aspects of the disease. So far 14 different KCNJ10 mutations have been published which either directly affect channel function or may lead to mislocalisation. Investigations of the pathophysiology may provide clues to potential treatments

Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome.

BACKGROUND: EAST syndrome is an autosomal recessive disorder caused by loss-of-function mutations in the gene KCNJ10. Among the 14 pathogenic mutations described so far, the p.R65P mutation stands out as the most frequent one and is particularly associated with patients of Pakistani origin. As a result we aimed to establish the existence of a potential founder effect in the Pakistani population. METHODS: To this end, we genotyped 12 patients from seven families and we compared disease haplotypes with ethnically matched control chromosomes. This haplotype was used together with demographic data for Pakistan to estimate the age of this founder mutation. RESULTS: We identified a small homozygous 0.694 Mb region around the KCNJ10 p.R65P mutation that had identical haplotypes in all of the patients which were completely absent in the control sample. Based on current demographic data and knowledge about disease frequency, we estimate that this particular p.R65P mutation arose 20 generations (about 500 years) ago. CONCLUSION: By knowing the prevalent mutation in a given population more efficient diagnostics can be performed and the families can benefit from specific counseling

An inexpensive method of small paraffin tissue microarrays using mechanical pencil tips

<p>Abstract</p> <p>Background</p> <p>Tissue microarray technology has provided a high throughput means of evaluating potential biomarkers in archival pathological specimens. This study was carried out in order to produce tissue microarray blocks using mechanical pencil tips without high cost.</p> <p>Method</p> <p>Conventional mechanical pencil tips (Rotring Tikky II Mechanical Pencil 1.0 mm) were used to cut out 1 mm wax cylinders from the recipient block, creating from 36 to 72 holes. Three cores of tumor areas were punched out manually by using the mechanical pencil tips from donor paraffin embedded tissue blocks and transferred to the holes of the paraffin tissue microarrays.</p> <p>Results</p> <p>This technique was easy and caused little damage to the donor blocks. We successfully performed H&E slides and immunodetection without substantial tissue cylinder loss.</p> <p>Conclusion</p> <p>Our mechanical pencil tip technique is the most inexpensive easy technique among the literature. It also takes a reasonable amount of time and reduces antibody consumption during immunohistochemistry</p

Hepatoprotective Effect of Captopril on Liver Toxicity Induced by High and Low Dose of Paracetamol in Rats:Histological Study

Many patients may administered medications like captopril (ACE inhibitor) for treatment of chronic diseases and may also take Paracetamol as an Over The Counter (OTC) drug which may interact with captopril. Therefore, the aim of this study is to evaluate of the hepatoprotective effect of captopril on liver toxicity induced by low and high dose of paracetamol in rats. This study was conducted in two phases: first study for low dose of paracetamol (300 mg/kg); animals were divided into 4 groups of 6 rats each (n = 6); all groups were treated orally either 0.9 % Normal Saline (NS), captopril 20 mg/kg, paracetamol 300 mg/kg or captopril 20 mg/kg plus paracetamol 300 mg/kg for 10 consecutive days. Second study for single high dose of paracetamol (3000 mg/kg); animals were divided into 4 groups of 6 rats each (n = 6); all groups were pretreated orally either 0.9 % Normal Saline (NS) or captopril 20 mg/kg for 7 consecutive days followed by single oral administration of Paracetamol 3000 mg/kg or normal saline. The administration of Paracetamol or normal saline was performed 24 hours after the last administration of captopril. After 48 hours of hepatic injury induction, the animals were then sacrificed and the liver was removed for histopathological studies. Low dose (300 mg/kg) for 10 days and high single dose (3000 mg/kg) of paracetamol produced hepatotoxic effects. While captopril 20 mg/kg showed marked protection against changes induced by low and high dose of paracetamol on the liver

Mitogenome Sequencing in the Genus Camelus Reveals Evidence for Purifying Selection and Long-term Divergence between Wild and Domestic Bactrian Camels

The genus Camelus is an interesting model to study adaptive evolution in the mitochondrial genome, as the three extant Old World camel species inhabit hot and low-altitude as well as cold and high-altitude deserts. We sequenced 24 camel mitogenomes and combined them with three previously published sequences to study the role of natural selection under different environmental pressure, and to advance our understanding of the evolutionary history of the genus Camelus. We confirmed the heterogeneity of divergence across different components of the electron transport system. Lineage-specific analysis of mitochondrial protein evolution revealed a significant effect of purifying selection in the concatenated protein-coding genes in domestic Bactrian camels. The estimated dN/dSPeer reviewe

Transformation of in-plane ρ(T)\rho (T) in YBa2Cu3O7−δYBa_{2}Cu_{3}O_{7-\delta} at fixed oxygen content

This paper reveals the origin of variation in the magnitude and temperature dependence of the normal state resistivity frequently observed in different YBCO single crystal or thin film samples with the same $T_{c}$. We investigated temperature dependence of resistivity in $YBa_{2}Cu_{3}O_{7-\delta}$ thin films with 7- $\delta = 6.95$ and 6.90, which were subjected to annealing in argon at 400-420 K ($120-140^{o}C$). Before annealing these films exhibited a non-linear $\rho_{ab}(T)$, with a flattening below 230 K, similar to $\rho_{b}(T)$ and $\rho_{ab}(T)$ observed in untwinned and twinned YBCO crystals, respectively. For all films the annealing causes an increase of resistivity and a transformation of $\rho_{ab}(T)$ from a non-linear dependence towards a more linear one (less flattening). In films with 7- $\delta = 6.90$ the increase of resistivity is also associated with an increase in $T_{c}$. We proposed the model that provides an explanation of these phenomena in terms of thermally activated redistribution of residual O(5) oxygens in the chain-layer of YBCO. Good agreement between the experimental data for $\rho_{ab}(t,T)$, where t is the annealing time, and numerical calculations was obtained.Comment: 8 pages, 9 figures, submitted to PR

Characteristics of Hospitalized Children With a Diagnosis of Malnutrition

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141004/1/jpen0623-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141004/2/jpen0623.pd

Learning beyond the classroom: students’ attitudes towards the integration of CLIL and museum-based pedagogies

In the last two decades, several studies have reported on the benefits of Content and Language Integrated Learning (CLIL) on students’ affective and cognitive gains. These studies, however, have mainly concentrated on the implementation of CLIL within the formal (school) context, with very little research on its impact in non-formal (out-of-school) contexts. Thus, the present article addresses this gap by describing an action research project aimed at understanding secondary school students’ attitudes towards the integration of CLIL and museum-based pedagogies. The project involved 284 students (14–16 years old) in northern Italy, who participated in a CLIL museum visit on Animal Classification through English at the Natural History Museum in Venice. A mixed-method research design was implemented and data was collected through students’ questionnaires and focus groups. Results reveal that students showed very positive attitudes towards taking part in a CLIL museum visit based on the interaction among the following dimensions: engagement with museum objects, use of English beyond the classroom, methodology and students’ interests, self-concept and career plans

Mobile ad hoc network testbed using mobile robot technology

MANET (Mobile Ad Hoc Network) researchers have shown increased interest in using mobile robot technology for their testbed platforms. Thus, the main motivation of this paper is to review various robot-based MANET testbeds that have been developed in previously reported research. Additionally, suggestions to heighten mobility mechanisms by using mobile robots to be more practical, easy and inexpensive are also included in this paper, as we unveils ToMRobot, a low-cost MANET robot created from an ordinary remote control car that is capable of performing a real system MANET testbed with the addition of only a few low-cost electronic components. Despite greatly reduced costs, the ToMRobot does not sacrifice any of the necessary MANET basic structures and will still be easily customizable and upgradeable through the use of open hardware technology like Cubieboard2 and Arduino, as its robot controller. This paper will also include guidelines to enable technically limited MANET researchers to design and develop the ToMRobot. It is hoped that this paper achieves its two pronged objectives namely (i) to facilitate other MANET researchers by providing them with a source of reference that eases their decision making for selecting the best and most suitable MANET mobile robots for real mobility in their MANET testbeds (ii) to provide MANET researchers with a prospect of building their own MANET robots that can be applied in their own MANET testbed in the future

A live weight-heart girth relationship for accurate dosing of east African shorthorn zebu cattle

The accurate estimation of livestock weights is important for many aspects of livestock management including nutrition, production and appropriate dosing of pharmaceuticals. Subtherapeutic dosing has been shown to accelerate pathogen resistance which can have subsequent widespread impacts. There are a number of published models for the prediction of live weight from morphometric measurements of cattle, but many of these models use measurements difficult to gather and include complicated age, size and gender stratification. In this paper, we use data from the Infectious Diseases of East Africa calf cohort study and additional data collected at local markets in western Kenya to develop a simple model based on heart girth circumference to predict live weight of east African shorthorn zebu (SHZ) cattle. SHZ cattle are widespread throughout eastern and southern Africa and are economically important multipurpose animals. We demonstrate model accuracy by splitting the data into training and validation subsets and comparing fitted and predicted values. The final model is weight0.262 =0.95 + 0.022 × girth which has an R2 value of 0.98 and 95 % prediction intervals that fall within the ±20 % body weight error band regarded as acceptable when dosing livestock. This model provides a highly reliable and accurate method for predicting weights of SHZ cattle using a single heart girth measurement which can be easily obtained with a tape measure in the field setting