Limitations of the Neurological Evolutional Exam (ENE) as a motor assessment for first graders

Background: Many clinicians and researchers in Brazil consider the Neurological Developmental Exam (NDE), a valid and reliable assessment for Brazilian school-aged children. However, since its inception, several tests have emerged that, according to some researchers, provide more in-depth evaluation of motor ability and go beyond the detection of general motor status (soft neurological signs). Objectives: To highlight the limitations of the NDE as a motor skill assessment for first graders. Methods: Thirty-five children were compared on seven selected items of the NDE, seven of the Bruininks-Oseretsky Test (BOT), and seven of the Visual-Motor Integration test (VMI). Participants received a 'pass' or 'fail' score for each item, as prescribed by the respective test manual. Results: Chi-square and ANOVA results indicated that the vast majority of children (74%) passed the NDE items, whereas values for the other tests were 29% (BOT) and 20% (VMI). Analysis of specific categories (e. g. visual, fine, and gross motor coordination) revealed a similar outcome. Conclusions: Our data suggest that while the NDE may be a valid and reliable test for the detection of general motor status, its use as a diagnostic/remedial tool for identifying motor ability is questionable. One of our recommendations is the consideration of a revised NDE in light of the current needs of clinicians and researchers.14537237

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through$800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of$400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from$714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of$50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al

Deletion Mutants of VPg Reveal New Cytopathology Determinants in a Picornavirus

BACKGROUND: Success of a viral infection requires that each infected cell delivers a sufficient number of infectious particles to allow new rounds of infection. In picornaviruses, viral replication is initiated by the viral polymerase and a viral-coded protein, termed VPg, that primes RNA synthesis. Foot-and-mouth disease virus (FMDV) is exceptional among picornaviruses in that its genome encodes 3 copies of VPg. Why FMDV encodes three VPgs is unknown. METHODOLOGY AND PRINCIPAL FINDINGS: we have constructed four mutant FMDVS that encode only one VPG: either VPg(1), VPg(3), or two chimeric versions containing part of VPg(1) and VPg(3). All mutants, except that encoding only VPg(1), were replication-competent. Unexpectedly, despite being replication-competent, the mutants did not form plaques on BHK-21 cell monolayers. The one-VPg mutant FMDVs released lower amounts of encapsidated viral RNA to the extracellular environment than wild type FMDV, suggesting that deficient plaque formation was associated with insufficient release of infectious progeny. Mutant FMDVs subjected to serial passages in BHK-21 cells regained plaque-forming capacity without modification of the number of copies of VPg. Substitutions in non-structural proteins 2C, 3A and VPg were associated with restoration of plaque formation. Specifically, replacement R55W in 2C was repeatedly found in several mutant viruses that had regained competence in plaque development. The effect of R55W in 2C was to mediate an increase in the extracellular viral RNA release without a detectable increase of total viral RNA that correlated with an enhanced capacity to alter and detach BHK-21 cells from the monolayer, the first stage of cell killing. CONCLUSIONS: The results link the VPg copies in the FMDV genome with the cytopathology capacity of the virus, and have unveiled yet another function of 2C: modulation of picornavirus cell-to-cell transmission. Implications for picornaviruses pathogenesis are discussed

Optimized DNA isolation from marine sponges for natural sampler DNA metabarcoding

Marine sponges have recently been recognized as natural samplers of environmental DNA (eDNA) due to their effective water filtration and their ubiquitous, sessile, and regenerative nature. However, laboratory workflows for metabarcoding of sponge tissue have not been optimized to ensure that these natural samplers achieve their full potential for community survey. We used a phased approach to investigate the influence of DNA isolation procedures on the biodiversity information recovered from sponges. In Phase 1, we compared three treatments of residual ethanol preservative in sponge tissue alongside five DNA extraction protocols. The results of Phase 1 informed which ethanol treatment and DNA extraction protocol should be used in Phase 2, where we assessed the effect of starting tissue mass on extraction success and whether homogenization of sponge tissue is required. Phase 1 results indicated that ethanol preservative may contain unique and/or additional biodiversity information to that present in sponge tissue, but blotting tissue dry generally recovered more taxa and generated more sequence reads from the wild sponge species. Tissue extraction protocols performed best in terms of DNA concentration, taxon richness, and proportional read counts, but the non-commercial tissue protocol was selected for Phase 2 due to cost-efficiency and greater recovery of target taxa. In Phase 2 overall, we found that homogenization may not be required for sponge tissue and more starting material does not necessarily improve taxon detection. These results combined provide an optimized DNA isolation procedure for sponges to enhance marine biodiversity assessment using natural sampler DNA metabarcoding

Impaired brain glymphatic flow in experimental hepatic encephalopathy

BACKGROUND AND AIMS: Neuronal function is exquisitely sensitive to alterations in extracellular environment. In patients with hepatic encephalopathy (HE), accumulation of metabolic waste products and noxious substances in the interstitial fluid of the brain is thought to be a consequence of the liver disease and may contribute to neuronal dysfunction and cognitive impairment. This study was designed to test the hypothesis that the accumulation of these substances, such as bile acids, may result from reduced clearance from the brain. METHODS: In a rat model of chronic liver disease with minimal HE (the bile duct ligation (BDL) model), we used emerging dynamic contrast-enhanced MRI and mass-spectroscopy techniques to assess the efficacy of the glymphatic system, which facilitates clearance of solutes from the brain. Immunofluorescence of aquaporin-4 (AQP4) and behavioural experiments were also performed. RESULTS: We identified discrete brain regions (olfactory bulb, prefrontal cortex and hippocampus) of altered glymphatic clearance in BDL rats, which aligned with cognitive/behavioural deficits. A significantly lower level of AQP4 expression was observed compared to the vasculature marker in both the olfactory bulb and prefrontal cortex in HE, which could be a contributing factor to the pathophysiological mechanisms underlying the impairment in glymphatic function observed in BDL rats. CONCLUSIONS: This study provides the first experimental evidence of impaired glymphatic flow in HE, potentially mediated by decreased AQP4 expression in the affected regions. LAY SUMMARY: The 'glymphatic system' is a newly discovered brain-wide pathway that facilitates clearance of various substances that accumulate in the brain due to its activity. This study evaluated whether the function of this system is altered in a model of brain dysfunction that occurs in cirrhosis. For the first time, we identified that the clearance of substances from the brain in cirrhosis is reduced because this clearance system is defective. This study proposes a new mechanism of brain dysfunction in patients with cirrhosis and provides new targets for therapy

Comparative Effectiveness of Guidelines for the Management of Hyperlipidemia and Hypertension for Type 2 Diabetes Patients

Background: Several guidelines to reduce cardiovascular risk in diabetes patients exist in North America, Europe, and Australia. Their ability to achieve this goal efficiently is unclear. Methods and Findings: Decision analysis was used to compare the efficiency and effectiveness of international contemporary guidelines for the management of hypertension and hyperlipidemia for patients aged 40-80 with type 2 diabetes. Measures of comparative effectiveness included the expected probability of a coronary or stroke event, incremental medication costs per event, and number-needed-to-treat (NNT) to prevent an event. All guidelines are equally effective, but they differ significantly in their medication costs. The range of NNT to prevent an event was small across guidelines (6.5-7.6 for males and 6.5-7.5 for females); a larger range of differences were observed for expected cost per event avoided (ranges, $117,269-$157,186 for males and $115,999-$163,775 for females). Australian and U.S. guidelines result in the highest and lowest expected costs, respectively. Conclusions: International guidelines based on the same evidence and seeking the same goal are similar in their effectiveness; however, there are large differences in expected medication costs. © 2011 Shah et al

Investigación de lateralidad en recién nacidos prematuros

O estudo objetivou investigar a existência de coordenação mão-boca e preferência manual em recém-nascidos (RNs) prematuros a partir da estimulação gustativa, comparando a lateralidade dos bebês e seus genitores. Trata-se de estudo experimental e analítico, com procedimento duplo-cego. Participaram 90 RNs prematuros de uma maternidade pública de Sergipe. O teste durou 15 minutos, dividido em 3 períodos de 5 minutos. Nos primeiros 5 minutos, linha de base inicial - LB1, nenhum estímulo foi aplicado. No segundo momento, houve estimulação gustativa com sacarose para análise (PA) a 12% ou água, em 5 doses de 0,2 mL a cada minuto; e no último período, linha de base final - LB2, houve observação do recém-nascido sem aplicação de estímulo, durante 5 minutos. Foi realizado registro da frequência e duração dos comportamentos das mãos direita (MBD) e/ou esquerda (MBE) na região oral e sucção das mãos direita (SMD) e/ou esquerda (SME) dos RNs durante os estados comportamentais (sono profundo, sono leve, sonolento, alerta, agitado/irritado e choro) apresentados por estes. Os dados foram executados no software Statistical Package for the Social Sciences. Como resultado encontrou-se correlação forte de MBD e SMD na LB2, independente do estímulo recebido, evidenciando que a estimulação aumentou a correlação dos comportamentos do lado direito do corpo. Sugere-se realização de novas pesquisas sobre lateralidade, contemplando maior número de pais sinistros na amostra. _________________________________________________________________________________________ RESUMEN: El objetivo del estudio fue investigar la existencia de coordinación mano-boca y la preferencia manual en recién nacidos prematuros a partir de la estimulación gustativa, comparando la lateralidad de los bebes y sus progenitores. Se trata de un estudio experimental y analítico, con procedimiento doble ciego. Participaron 90 recién nacidos prematuros de una maternidad pública de Sergipe. El test duró 15 minutos, dividido en tres períodos de cinco minutos. En los primeros cinco minutos, línea de base inicial - LB1, ningún estímulo fue aplicado. En un segundo momento, existió estimulación gustativa con sacarosa PA a 12% o agua, en cinco dosis de 0,2 mL a cada minuto, y en el último período, línea de base final - LB2, existió observación del recién nacido sin aplicación de estímulo, durante cinco minutos. Fue realizado registro de la frecuencia y duración de los comportamientos en la mano derecha (MBD) y/o mano izquierda (MBI) en la región oral y succión de la mano derecha (SMD) y/o izquierda (SMI) de los recién nacidos durante los estados comportamentales (sueño profundo, sueño leve, somnoliento, alerta, agitado/irritado y llanto) presentados por estos. Los datos fueron analizados en el software Stastistical Package for the Social Sciences. Como resultado se encontró correlación fuerte de MBD y SMD en la LB2, independiente del estímulo recibido, evidenciando que la estimulación aumentó la correlación de los comportamientos del lado derecho del cuerpo. Se sugiere realización de nuevas investigaciones sobre lateralidad, contemplando mayor número de padres zurdos en la muestra