Review of topiramate for the treatment of epilepsy in elderly patients

Individuals over 65 years of age experience the new onset of seizures at a prevalence rate of roughly twice that of younger adults. Differences in physiology, need of concomitant medications, and liability for cognitive deficits in this population, make the choice of anticonvulsant drugs especially important. This paper reviews topiramate (TPM), a treatment for many types of seizures, with the above risks in mind. In particular, we discuss efficacy and pharmacokinetics with emphasis on the older patient, and adverse events in both the younger and older adult. With most studies of TPM-induced cognitive deficits having been performed in younger adults and volunteers, we discuss the implications for the older adult. Even in studies of younger individuals, up to 50% discontinue TPM because of intolerable cognitive deficits. Most studies find specific declines in working memory and verbal fluency. In conclusion, we give recommendations for use of this antiepileptic drug in this population

The survey of serum retinol of the children aged 0~4 years in Zhejiang Province, China

<p>Abstract</p> <p>Background</p> <p>Vitamin A can have a positive impact on growth and development of children, but vitamin A deficiency (VAD) was found to be a public health problem in Zhejiang Province, China in 1998. There have been no studies on this topic in Zhejiang Province recently. This study was designed to evaluate the serum retinol levels of children aged 0~4 years in Zhejiang Province, southeast China. This epidemiological data will help design supplementation strategies for vitamin A in high-risk groups and improve their vitamin A status.</p> <p>Methods</p> <p>Children were randomly recruited for this study using a stratified sampling method. A blood sample was collected from each child. Assessment included C-reactive protein (CRP), serum retinol measured with HPLC and a questionnaire completed providing for family information and nutritional status. Logistic regression analysis was used to evaluate the risk factors for VAD in children.</p> <p>Results</p> <p>A group of 357 subjects aged 1 day to 4 years were recruited. The mean plasma retinol concentration was 1.653 (sd 0.47) μmol/L. There were 3.08% (11/357) of children affected with VAD, and 7.28% (26/357) of children had low vitamin A status, but none of the children showed any clinical symptoms of VAD. There was no significant difference in the levels of plasma retinol and the incidence rate of VAD between male and female children. Multivariate logistic regression analysis showed that living in urban region, having parents with good education and taking vitamin A capsule regularly prevented children from VAD, whereas being young (less than 2 years old) was a risk factor.</p> <p>Conclusion</p> <p>Low vitamin A status remains a nutritional problem in Zhejiang Province. The high-risk group in this study were young, dwelled in rural regions, had parents with poor education and did not take a regular vitamin A containing supplement.</p

Cold gas accretion in galaxies

Evidence for the accretion of cold gas in galaxies has been rapidly accumulating in the past years. HI observations of galaxies and their environment have brought to light new facts and phenomena which are evidence of ongoing or recent accretion: 1) A large number of galaxies are accompanied by gas-rich dwarfs or are surrounded by HI cloud complexes, tails and filaments. It may be regarded as direct evidence of cold gas accretion in the local universe. It is probably the same kind of phenomenon of material infall as the stellar streams observed in the halos of our galaxy and M31. 2) Considerable amounts of extra-planar HI have been found in nearby spiral galaxies. While a large fraction of this gas is produced by galactic fountains, it is likely that a part of it is of extragalactic origin. 3) Spirals are known to have extended and warped outer layers of HI. It is not clear how these have formed, and how and for how long the warps can be sustained. Gas infall has been proposed as the origin. 4) The majority of galactic disks are lopsided in their morphology as well as in their kinematics. Also here recent accretion has been advocated as a possible cause. In our view, accretion takes place both through the arrival and merging of gas-rich satellites and through gas infall from the intergalactic medium (IGM). The infall may have observable effects on the disk such as bursts of star formation and lopsidedness. We infer a mean ``visible'' accretion rate of cold gas in galaxies of at least 0.2 Msol/yr. In order to reach the accretion rates needed to sustain the observed star formation (~1 Msol/yr), additional infall of large amounts of gas from the IGM seems to be required.Comment: To appear in Astronomy & Astrophysics Reviews. 34 pages. Full-resolution version available at http://www.astron.nl/~oosterlo/accretionRevie

Spectroscopic investigations of a semi-synthetic [FeFe] hydrogenase with propane di-selenol as bridging ligand in the binuclear subsite: comparison to the wild type and propane di-thiol variants

[FeFe] Hydrogenases catalyze the reversible conversion of H2 into electrons and protons. Their catalytic site, the H-cluster, contains a generic [4Fe–4S]H cluster coupled to a [2Fe]H subsite [Fe2(ADT)(CO)3(CN)2]2−, ADT = µ(SCH2)2NH. Heterologously expressed [FeFe] hydrogenases (apo-hydrogenase) lack the [2Fe]H unit, but this can be incorporated through artificial maturation with a synthetic precursor [Fe2(ADT)(CO)4(CN)2]2−. Maturation with a [2Fe] complex in which the essential ADT amine moiety has been replaced by CH2 (PDT = propane-dithiolate) results in a low activity enzyme with structural and spectroscopic properties similar to those of the native enzyme, but with simplified redox behavior. Here, we study the effect of sulfur-to-selenium (S-to-Se) substitution in the bridging PDT ligand incorporated in the [FeFe] hydrogenase HydA1 from Chlamydomonas reinhardtii using magnetic resonance (EPR, NMR), FTIR and spectroelectrochemistry. The resulting HydA1-PDSe enzyme shows the same redox behavior as the parent HydA1-PDT. In addition, a state is observed in which extraneous CO is bound to the open coordination site of the [2Fe]H unit. This state was previously observed only in the native enzyme HydA1-ADT and not in HydA1-PDT. The spectroscopic features and redox behavior of HydA1-PDSe, resulting from maturation with [Fe2(PDSe)(CO)4(CN)2]2−, are discussed in terms of spin and charge density shifts and provide interesting insight into the electronic structure of the H-cluster. We also studied the effect of S-to-Se substitution in the [4Fe–4S] subcluster. The reduced form of HydA1 containing only the [4Fe–4Se]H cluster shows a characteristic S = 7/2 spin state which converts back into the S = 1/2 spin state upon maturation with a [2Fe]–PDT/ADT complex

Differential predictors of acute post-surgical pain intensity after abdominal hysterectomy and major joint arthroplasty

Author's personal copyBACKGROUND Psychological factors have a significant role in post-surgical pain, and their study can inform pain management. PURPOSE The aims of this study are to identify psychological predictors of post-surgical pain following abdominal hysterectomy (AH) and major joint arthroplasty (MJA) and to investigate differential predictors by type of surgery. METHOD One hundred forty-two women undergoing AH and 110 patients undergoing MJA were assessed 24 h before (T1) and 48 h after (T2) surgery. RESULTS A predictive post-surgical pain model was found for AH and MJA yielding pre-surgical pain experience and pain catastrophizing as significant predictors and a significant interaction of pre-surgical optimism and surgery type. Separate regression models by surgery type showed that pre-surgical optimism was the best predictor of post-surgical pain after MJA, but not after AH. CONCLUSIONS Findings highlight the relevance of psychological predictors for both surgeries and the value of targeting specific psychological factors by surgery type in order to effectively manage acute post-surgical pain.Supported by a project grant (PTDC/SAU-NEU/108557/2008) and by a PhD grant (SFRH/BD/36368/2007) from the Portuguese Foundation of Science and Technology, COMPETE, and FEDE

Catalytic living ring-opening metathesis polymerization

In living ring-opening metathesis polymerization (ROMP), a transition-metal–carbene complex polymerizes ring-strained olefins with very good control of the molecular weight of the resulting polymers. Because one molecule of the initiator is required for each polymer chain, however, this type of polymerization is expensive for widespread use. We have now designed a chain-transfer agent (CTA) capable of reducing the required amount of metal complex while still maintaining full control over the living polymerization process. This new method introduces a degenerative transfer process to ROMP. We demonstrate that substituted cyclohexene rings are good CTAs, and thereby preserve the ‘living’ character of the polymerization using catalytic quantities of the metal complex. The resulting polymers show characteristics of a living polymerization, namely narrow molecular-weight distribution, controlled molecular weights and block copolymer formation. This new technique provides access to well- defined polymers for industrial, biomedical and academic use at a fraction of the current costs and significantly reduced levels of residual ruthenium catalyst

Processing of Genome 5′ Termini as a Strategy of Negative-Strand RNA Viruses to Avoid RIG-I-Dependent Interferon Induction

Innate immunity is critically dependent on the rapid production of interferon in response to intruding viruses. The intracellular pathogen recognition receptors RIG-I and MDA5 are essential for interferon induction by viral RNAs containing 5′ triphosphates or double-stranded structures, respectively. Viruses with a negative-stranded RNA genome are an important group of pathogens causing emerging and re-emerging diseases. We investigated the ability of genomic RNAs from substantial representatives of this virus group to induce interferon via RIG-I or MDA5. RNAs isolated from particles of Ebola virus, Nipah virus, Lassa virus, and Rift Valley fever virus strongly activated the interferon-beta promoter. Knockdown experiments demonstrated that interferon induction depended on RIG-I, but not MDA5, and phosphatase treatment revealed a requirement for the RNA 5′ triphosphate group. In contrast, genomic RNAs of Hantaan virus, Crimean-Congo hemorrhagic fever virus and Borna disease virus did not trigger interferon induction. Sensitivity of these RNAs to a 5′ monophosphate-specific exonuclease indicates that the RIG-I-activating 5′ triphosphate group was removed post-transcriptionally by a viral function. Consequently, RIG-I is unable to bind the RNAs of Hantaan virus, Crimean-Congo hemorrhagic fever virus and Borna disease virus. These results establish RIG-I as a major intracellular recognition receptor for the genome of most negative-strand RNA viruses and define the cleavage of triphosphates at the RNA 5′ end as a strategy of viruses to evade the innate immune response

Evidence for the ‘Good Genes’ Model: Association of MHC Class II DRB Alleles with Ectoparasitism and Reproductive State in the Neotropical Lesser Bulldog Bat, Noctilio albiventris

The adaptive immune system has a major impact on parasite resistance and life history strategies. Immunological defence is costly both in terms of immediate activation and long-term maintenance. The ‘good genes’ model predicts that males with genotypes that promote a good disease resistance have the ability to allocate more resources to reproductive effort which favours the transmission of good alleles into future generations. Our study shows a correlation between immune gene constitution (Major Histocompatibility Complex, MHC class II DRB), ectoparasite loads (ticks and bat flies) and the reproductive state in a neotropical bat, Noctilio albiventris. Infestation rates with ectoparasites were linked to specific Noal-DRB alleles, differed among roosts, increased with body size and co-varied with reproductive state particularly in males. Non-reproductive adult males were more infested with ectoparasites than reproductively active males, and they had more often an allele (Noal-DRB*02) associated with a higher tick infestation than reproductively active males or subadults. We conclude that the individual immune gene constitution affects ectoparasite susceptibility, and contributes to fitness relevant trade-offs in male N. albiventris as suggested by the ‘good genes’ model

Potential interventions for the prevention of childhood pneumonia in developing countries: a meta-analysis of data from field trials to assess the impact of vitamin A supplementation on pneumonia morbidity and mortality. The Vitamin A and Pneumonia Working Group.

Reported are the results of a meta-analysis (12 large-scale field trials in seven countries) of the impact of vitamin A supplementation on pneumonia morbidity and mortality, undertaken as part of a wider review process of a range of possible potential interventions for the prevention of childhood pneumonia. The summary estimate of the relative risk for the impact of vitamin A supplementation on pneumonia incidence was 0.95 (95% confidence interval (CI) = 0.89, 1.01), and for pneumonia mortality, 0.98 (95% CI = 0.75, 1.28). This is in marked contrast to the substantial impact of vitamin A supplementation on all-cause mortality (combined rate ratio (RR) = 0.77, 95% CI = 0.71, 0.84), and on diarrhoea-specific and measles-specific mortality. There was no evidence for a differential impact on pneumonia mortality by age. Since the majority of pneumonia deaths occur in the first year of life, we complemented the paucity of data on pneumonia-specific mortality among this age group with a detailed examination of all-cause mortality among infants. The mortality reduction in the 6-11 month age group was consistent with that observed for older age groups (RR = 0.69; 95% CI = 0.54, 0.90), but there was no reduction for 0-5 month-olds (RR = 0.97; 95% CI = 0.73, 1.29)

Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology

OBJECTIVE: Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines. METHODS: A systematic review of randomized antipsychotic clinical trials in treatment-resistant schizophrenia was performed, and definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed through 1) a multiphase, mixed methods approach, 2) identification of key criteria via an online survey, and 3) meetings to achieve consensus. RESULTS: Of 2,808 studies identified, 42 met inclusion criteria. Of these, 21 studies (50%) did not provide operationalized criteria. In the remaining studies, criteria varied considerably, particularly regarding symptom severity, prior treatment duration, and antipsychotic dosage thresholds; only two studies (5%) utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current symptoms of a minimum duration and severity determined by a standardized rating scale; 2) moderate or worse functional impairment; 3) prior treatment consisting of at least two different antipsychotic trials, each for a minimum duration and dosage; 4) systematic monitoring of adherence and meeting of minimum adherence criteria; 5) ideally at least one prospective treatment trial; and 6) criteria that clearly separate responsive from treatment-resistant patients. CONCLUSIONS: There is considerable variation in current approaches to defining treatment resistance in schizophrenia. The authors present consensus guidelines that operationalize criteria for determining and reporting treatment resistance, adequate treatment, and treatment response, providing a benchmark for research and clinical translation