Development of oral immunomodulatory agents in the management of multiple sclerosis

The emergence of oral disease-modifying therapies in multiple sclerosis (MS) will have a significant impact on the evolving scenario of immunomodulatory treatments in MS where current therapies are all injectable. Reducing relapses in trials translates for individuals with MS into a therapeutic aim of stopping future events. Thus the possible absence of any perceived benefits to the individual together with the long disease course, variable outcome, and a younger age group affected in MS makes side effects the major issue. The use of disease-modifying therapies as a whole needs to be placed in the context of a widening therapeutic indication where the use of these therapies is being justified at an increasingly early stage and in pre-MS syndromes such as clinically isolated and radiologically isolated syndromes where no fixed disability is likely to have accumulated. The five oral therapies discussed (cladribine, fingolimod, laquinimod, BG-12, and teriflunomide) have just completed Phase III studies and some have just been licensed. New oral drugs for MS need to be placed within this evolving marketplace where ease of delivery together with efficacy and side effects needs to be balanced against the known issues but also the known long-term safety of standard injectables

Overview of ICTs and health

Open access journal.Community informatics links economic and social development efforts at the community level with emerging opportunities in Information and Communication Technologies (ICTs). In recent years in public health there has been an increased focus on the broader social determinants of health and on social inclusion, as evidenced in the 2008 Final Report of the Commission on Social Determinants of Health1. Broader determinants include education, income, social connection, and other opportunities that support improved health and wellbeing

Identification and determination of antibiotic resistance of pathogenic bacteria Isolated from Septic Wounds

Wound infection is a global cause of morbidity and mortality across all wound types. Therefore, efficient diagnosis and treatment of wound infection are essential. This study was carried out to identify the pathogenic bacteria in infected wounds of the patient’s attending Sebha city hospitals (Libya) and to determine their resistance profile to the most common antibiotics used in therapy. A total of sixty wound swab specimens were collected and cultured, of which 39 samples showed bacterial growth. Three different species of bacteria were isolated. Staphylococcus aureus 21 (53.9%) were the most common organisms followed by Pseudomonas aeruginosa 10 (25.6%) and Staphylococcus epidermidis 8 (20.5%). The antibiotic susceptibility test of the bacterial isolate was performed by Kirby-Bauer disk diffusion method. Results showed that 90.5% of the Staphylococcus aureus isolates were resistant to vancomycin, 61.9% to tetracycline, 57.1% to amoxicillin, 52.4 % to methicillin, 42.9 to erythromycin and 23.8% to streptomycin. 87.5% of the Staphylococcus epidermidis isolates were resistant to vancomycin, 75% to methicillin, 62.5% to tetracycline, 50% to streptomycin 37.5% to amoxicillin, and erythromycin. All the Pseudomonas aeruginosa isolates were sensitive to ciprofloxacin and highly resistant 90-100% to other antibiotics tested Amoxicillin, Nalidixic acid, Streptomycin, and Tetracycline. The high rate of multiple antibiotic resistance was observed in all bacterial species recovered

Adenylosuccinate lyase deficiency- a cause of seizures in children: Development of an assay for its diagnosis

Adenylosuccinate Lyase (ADSL) Deficiency is one of the rare causes of neonatal and infantile seizures. This condition results from autosomal recessive mutations in the gene coding for the enzyme ADSL, mapped to human chromosome 22ql3.1-13.2. The ADSL enzyme plays an important role in the de novo pathways of purine metabolism and thus deficiency, and/ or decreased catalytic activity of this enzyme is manifested in form of repeated seizures in early childhood. Other neurological symptoms and signs may be present, such as psychomotor retardation, autistic features, axial and peripheral hypotonia, and muscle atrophy and secondary feeding problems leading to severe growth retardation. Although ADSL deficiency is considered a rare cause of childhood epilepsy and only 50 cases have been reported till now world wide, the magnitude of the problem can not be determined unless rapid accurate diagnostic test is introduced, especially, in communities with high rate of consanguinity. Fortunately, several reports have given a hint for Succinyladenosine or S-Ado as a new promising diagnostic marker for this disorder. This information may have enormous impact in the era of enzyme replacement therapy and thus this condition could be to some extent preventable, once proper genetic counseling and testing for carriers of the mutations in families with this condition is possible. In the present study we aimed to develop and validate a new HPLC method for the detection of S-Ado in the CSF. Material and Methods HPLC system with anion exchange Sphere Clone 5u SAX (250 x 4.6) has been developed using synthetic S-Ado in different concentrations to obtain the linear calibration curve. A total of 23 CSF samples were obtained from 23 patients, 12 females (52.2%), 11 male (47.8%), age ranging between 1-16 years, are processed for measurement of S-Ado using the currently developed HPLC system. All patients were referred to the Neurometabolic unit at the National Hospital for Neurology and Neurosurgery during the year 2005 with seizures except 2 samples form known ADSL deficiency male patients received as gift from Dr. Keith Hyland (Horizon Molecular Medicine, Atlanta, GA, USA). We considered the presence of RBCs or hemolysis in the CSF as exclusion criteria. Outcome and Results A rapid, accurate, in addition sensitive and specific HPLC system with anion exchange SAX column, to detect S-Ado in CSF of patients with ADSL deficiency has been successfully developed and validated. The total time for the test < 15 minutes, and the method validation was achieved by measuring the S-Ado concentration in the CSF of 21 unknown patients presented to the Neurometabolic unit, the observed S-Ado reference range concentration for these cases was found to be varying between (0.55 to 2.36uM). None of the randomly selected disease control cases showed an abnormal S-Ado concentration, whereas the two CSF samples for known cases of ADSL deficiency have shown very high concentrations (356.8 and 357.1 iM) of S-Ado compared with non-ADSL patients. Recovery of S-Ado from spiked CSF after addition of a known concentration (10M) was achieved by with very high accuracy (range 92%-100%)i.e. greater than 98% in average .The physical properties of S-Ado were found to be stable substance in different and wide range of store temperature i.e. in (-80 C) and also when stored at room temperature (20.8 C), for more than 24 hours .Thus an age related reference range was established for S-Ado in the CSF and the statistical analysis showed no significant cumulative effect of the age or the sex on this reference range. The study was completed within total of 3 month duration, and mean intraday variation was 5% and the interday variation was < 10%. Conclusion: the current method is sensitive specific and enables rapid reliable detection of S-Ado in the CSF of patient with ADSL deficiency in < 15 mi

Aspen forests on the Uncompahgre Plateau: current and future expectations

2012 Fall.Includes bibliographical references.Dynamic changes in aspen cover on the Uncompahgre Plateau have raised concerns among researchers and communities about the stability and long-term survivorship of aspen forests. In the summer of 2010, aspen increment cores were measured for current age distribution from sixty-three random locations across the Plateau including pure aspen and mixed conifer- aspen stands, to provide insights about aspen forests in the near future. Most of aspen trees on the Plateau in 2010 were 100 to 130 years old, and having established after the last major landscape-scale fire in 1879. Trees older than 140 years accounted for about 2% of all stems, with the oldest tree in our random sample being 272 years at breast height. Aspen cover will likely decline over the next five decades, as young cohorts (<80 years) have fewer stems than older cohorts (100- 130 years). Several ecological processes or events could accelerate aspen decline, including conifer replacement of aspens in mixed stands and severe drought. The three survivorship scenarios showed that the reduction in aspen cover by 2060 will likely vary from about 40% of current aspen cover in the most optimistic scenario to a 84% reduction in a higher mortality scenario. The Plateau currently has abundant numbers of aspen suckers, but few of these escape browsing pressure to become trees. The aspen decline predicted in the scenarios may continue beyond 2060 if recruitment remains low, or could be turned around if widespread disturbance regenerates forests, or if browsing pressure drops substantially

Overview of ICTs and Health

Community informatics links economic and social development efforts at the community level with emerging opportunities in Information and Communication Technologies (ICTs). In recent years in public health there has been an increased focus on the broader social determinants of health and on social inclusion, as evidenced in the 2008 Final Report of the Commission on Social Determinants of Health1. Broader determinants include education, income, social connection, and other opportunities that support improved health and wellbeing

A systematic approach for evaluating the accuracy of overhead line fault location using the traveling wave method

In the power system, the high-voltage transmission lines are responsible for transmitting large amounts of energy from one location to another. However, this feature is not always possible because of different defects that may occur on these lines. Therefore, power suppliers must provide exact defective locations where maintenance lines can accelerate, system reliability improved, and unnecessary operating expenses eliminated. In this paper, the traveling wave technique based on wavelet transform proposes to find the exact location assist with voltages and currents signal at the single and multi-end of the transmission line. The techniques simulated using PSCAD / EMTDC software based on a single-phase to ground fault and tested on the sample system. A compendium of the results has shown that the multi-end technique is more accurate than the single-end technique

COGNITIVE AND NEUROPSYCHIATRIC STATUS IN A LARGE COHORT OF PATIENTS WITH SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS The combined influence of parental education and preterm birth on school performance

Background Social background and birth characteristics are generally found to be independently associated with school achievements but the underlying mechanisms are not fully understood. This study aimed to explore how parental education and shorter gestational age jointly influence school performance in a cohort of Swedish children. Methods 10 835 children born between 1973 and 1981 were studied, the third generation of the register-based Uppsala Multigenerational Birth Cohort. Ordinal logistic regression models were fitted to estimate OR of achieving middle and high grades in Swedish language at age 16 years, relative to low grade, by parental education and own gestational age, adjusting for potential confounders. Results In children from families with lower parental education, the adjusted OR of receiving a higher grade was 0.54 (95% CI 0.41 to 0.71) for preterm (<37 completed weeks) compared with full-term births. This estimate did not change when adjusted for several potential confounders (0.59; CI 0.44 to 0.79). When different cut-points were selected to define preterm birth, the estimated OR for those with low parental education decreased linearly from 0.83 (CI 0.72 to 0.96) using less than 39 weeks as the cut-point, to 0.52 (CI 0.30 to 0.90) using less than 35 weeks. There was no evidence of significant effects of shorter gestational age for children with parents from other educational groups. Conclusions The disadvantage of shorter gestational age on the chance of achieving higher grades in Swedish language was confined to children from families in which none of the parents had higher education. This suggests that the detrimental influence of shorter gestational age on school performance in language may be avoidable