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Background: Several studies on clinical practice for Duchenne muscular dystrophy (DMD) have been conducted in Western countries. However, there have been only a few similar studies in Asia and Oceania. Here, we investigate the steroid therapy-related clinical practice for DMD among the local experts. In 2015, we conducted a DMD expert survey in Asia and Oceania to acquire information regarding patients with DMD and to assess current clinical practice with the cooperation of Asian and Oceanian Myology Centre, a neuromuscular disease research network. Results: We obtained survey responses from 87 out of 148 clinicians (62%) from 13 countries and regions. In China, 1385 DMD patients were followed-up by 5 respondent neurologists, and 84% were between 0 and 9 years of age (15% were 10-19 years, 1% > 19 years). While in Japan, 1032 patients were followed-up by 20 clinicians, and the age distribution was similar between the 3 groups (27% were 0-9 years, 35% were 10-19 years, 38% were >19 years). Most respondent clinicians (91%) were aware of DMD standard of care recommendations. Daily prednisolone/prednisone administration was used most frequently at initiation (N = 45, 64%). Inconsistent opinion on steroid therapy after loss of ambulation and medication for bone protection was observed. Conclusions: Rare disease research infrastructures have been underdeveloped in many of Asian and Oceanian countries. In this situation, our results show the snapshots of current medical situation and clinical practice in DMD. For further epidemiological studies, expansion of DMD registries is necessary Refereed/Peer-reviewed

1·8 billion people of diverse ethnicities and cultures live in the Western Pacific Region. The increasing longevity of populations in this region is a major contributor to the exponential increase in Parkinson's disease prevalence worldwide. Differences exist between Parkinson's disease in the Western Pacific Region and in Europe and North America that might provide important insights into our understanding of the disease and approaches to management. For example, some genetic factors (such as LRRK2 mutations or variants) differ, environmental exposures might play differential roles in modulating the risk of Parkinson's disease, and fewer dyskinesias are reported, with some differences in the profile of non-motor symptoms and comorbidities. Gaps in awareness of the disease and inequitable access to treatments pose challenges. Further improvements in infrastructure, clinical governance, and services, and concerted collaborative efforts in training and research, including greater representation of the Western Pacific Region in clinical trials, will improve care of patients with Parkinson's disease in this region and beyond.

Resumen Objetivo El objetivo de este estudio es evaluar el tamano de la glena en una poblacion espanola normal, compararla con resultados previos en otras poblaciones y relacionarlo con los tamanos de implante que se comercializan para la artroplastia invertida de hombro. Material y metodos Estudio antropometrico de la glena humana utilizando tomografias computarizadas de 154 pacientes con edades superiores a 30 anos, realizados entre enero de 2015 y diciembre de 2017. Se valoran tomografias computarizadas de hombro con cortes de 2 mm de grosor y 0 mm de intervalo entre cortes, en algoritmo oseo y de partes blandas, realizandose reconstruccion 3 D sobre la cual se obtienen mediciones de longitud y anchura de la glena. El punto superior de la glena se determino en la zona superior del ovoide de la glena, en el tuberculo supraglenoideo, justo por debajo del reborde circunferencial que rodea la glena. El punto inferior se determino como el punto mas alejado del punto superior en el contorno de la glena, a nivel superior del reborde circunferencial que rodea la glena. Los puntos anterior y posterior fueron determinados como los extremos del eje transversal mayor en un plano perpendicular al eje superoinferior, por dentro del reborde circunferencial que rodea la glena. Las diferencias entre sexos, edad, altura, peso y relaciones de tamanos fueron evaluados. Resultados La glena tiene un eje longitudinal medio de 28,78 mm y una anchura de 20,27 mm. Los valores del tamano de la glena son significativamente diferentes en hombres y mujeres, siendo mayor en hombres. El tamano de la glena esta bien correlacionado con la estatura del paciente, existiendo una asociacion positiva entre la estatura y la longitud y anchura de la superficie glenoidea. Las metaglenas circulares disponibles hoy en el mercado presentan tamanos no inferiores a 24-25 mm de diametro. Conclusion La poblacion del sur de Espana presenta un tamano de la superficie glenoidea inferior a la poblacion americana y semejante a la cohorte asiatica. Los datos antropometricos expresados pueden ser utiles para la eleccion de la metaglena mas apropiada en la poblacion del sur de Espana.

Objective To evaluate the size of the glenoid in a southern Spanish population, to compare it with previous results from other populations and determine the size of the implants that are marketed for shoulder arthroplasty. Material and methods Between January 2015 and December 2017, an anthropometrical study of the human glenoid was performed using computed axial tomography scans (CT) of 154 patients over 30 years old. The glenoid dimensions were analysed 3-dimensionally using 2 mm interval thicknesses, determining the average height and width of the glenoid. The upper point of the glenoid geometry was determined as the supraglenoid tubercle of the ovoid glenoid surface, where the long head of the biceps tendon is thought to originate. The lower point was then positioned at the furthest point from the upper point on the glenoid contour. Anterior and posterior points were determined such that the 3-dimensional anterior–posterior distance was maximised on the plane perpendicular to the upper–lower axis. Sex differences and correlations between sides and among the respective parameters in the glenohumeral dimensions were also evaluated. Results The glenoid had an average height of 28.78 mm and width of 20.27 mm. The values were significantly different between the men and the women, being greater in the men. The glenoid size is well correlated with the patient's size. Direct correlations exist between the glenoid height and width and the glenoid size and the patient's height. The available metaglenoids currently on the market are no bigger than 25–24 mm. Conclusion In comparison, the southern Spanish population have a glenoid size similar to the Caucasian population, but smaller than that of the American population. The data shown could be useful to improve the design of shoulder prostheses for the southern Spanish population.

Background X-linked dystonia-parkinsonism (XDP) is characterized by the unique transition of dystonia to parkinsonism and striatal degeneration. Slowing of saccades on clinical examination has been taken as suggestive of a progressive supranuclear palsy (PSP) phenotype. Objectives To elucidate whether eye movement abnormalities in XDP patients reflect striatonigral impairment or deficits in the brainstem saccade generator as present in PSP. Methods Eye movements of 18 male XDP patients from the Philippines and 16 ethnically and age-matched, healthy control participants were analyzed and the results related to morphometric frontostriatal changes. Results There was moderate saccade hypometria in XDP but velocity of visually guided saccades was normal. XDP patients showed an increased antisaccade error rate which correlated with the reduction of (i) the volume of the pallidum and putamen as well as (ii) the volume and cortical thickness in dorsolateral prefrontal cortex. Amplitude of memory-guided saccades was smaller and latency prolonged. Horizontal smooth pursuit eye movements were impaired. Conclusions Oculomotor abnormalities in XDP resemble those of patients with the Parkinsonian type of multiple system atrophy and - to a lesser degree - Parkinson's disease, but are not compatible with PSP. They indicate striatal impairment and may represent preclinical signs of the parkinsonian stage of XDP. The increasing failure of response inhibition in the antisaccade task with increasing striatal atrophy may indicate an endophenotype for striatal degeneration. Dorsolateral prefrontal degeneration can be inferred from the failure in initiating antisaccades, prolonged latency of memory-guided saccades and the reduction of dorsolateral prefrontal volume and cortical thickness.

Prevalence of Parkinson's Disease (PD) in the Philippines has been estimated to be 1 % based on a 2007 nationwide survey conducted by the Philippine Neurological Association, but without case ascertainment. Since there is still paucity of data, we aim to determine the prevalence of PD in a rural community and the possible predisposing factors on the development of the disease.This is a two-phase descriptive study which investigated the prevalence of PD and associated risk factors in a randomly selected rural community in Candelaria, Quezon Province. A validated screening questionnaire was utilized, and case ascertainment was done in eligible respondents.A total of 365 respondents aged ≥ 20 years were randomly surveyed from 2016 to 2017. Two cases of PD aged ≥ 60 years were reported. Thus, the prevalence of PD in the community was 0.55 %. Age-specific prevalence of PD among individuals ≥ 60 years was 4.35 %.Insecticide use was infrequent in the community and was recorded in one PD patient. Protective factors like smoking and drinking tea were not observed in both cases whereas coffee intake was reported in one PD patient.This community-based epidemiologic study on PD is consistent with a nationwide study. The study portrayed certain demographic and environmental features inherent in a community, which are potential confounding variables in PD development. Future larger population studies be recommended to establish PD in the advancing age and to further support the link of various factors with PD.

Oromandibular dystonia (OMD) is a severely disabling disorder with limited available therapies. Current oral medications for OMD are ineffective and may pose further risks of aspiration particularly in combination states of jaw and tongue dystonia. We advocate the use of Botulinum neurotoxin (BoNT) injection with proper muscle site selection and dosing as the most effective treatment in OMD clinically. Targeting muscle for injection should involve not only an astute clinical examination and understanding the patient’s history, but perhaps also guided by instrumentation. Based on our previous and present case series, we present specific localization techniques for BoNT in OMD patients subsequent to methodical patient selection, proper BoNT reconstitution and conversion. We believe adequate knowledge and appropriate technique will give our patients greatest benefit and will minimize risk of adverse events following treatment.

In this session, Dr Raymond Rosales discusses on the role of focal botulinum toxin injections in movement disorders.

Introduction X-linked recessive dystonia-parkinsonism (XDP, DYT3) is highly prevalent in the Philippines and manifests with varying phenotype. We sought to evaluate the significance of transcranial brain sonography as a biomarker for parkinsonism-predominant phenotype. Methods 90 Filipino participants were enrolled into a cross-sectional study: 39 patients with XDP, 21 asymptomatic first-degree relatives of XDP patients, and 30 healthy control subjects. Echogenicity of the substantia nigra and the lenticular nuclei was digitally quantified. Brain sonography data were compared with video-based clinical assessment, genetic status and pedigree charts. Results The majority of patients had hyperechogenicity of the substantia nigra (79%) and/or the lenticular nuclei (81%). Disease duration correlated with echointensity of lenticular nuclei (Pearson test, r = 0.55, p = 0.029) but not substantia nigra (p = 0.31). Abnormal substantia-nigra hyperechogenicity was more frequent in patients with prominent parkinsonism (100%) compared to those without (68%; χ2 test, p = 0.035). The grading of substantia-nigra echogenicity (normal/increased) in patients was in all cases identical to that in their respective asymptomatic relatives. All patients with “familial” substantia-nigra normoechogenicity presented with a phenotype of predominant dystonia and only mild parkinsonism. In turn, “familial” substantia-nigra hyperechogenicity indicated a phenotype with moderate to severe parkinsonism (sensitivity, 100%; specificity, 67%; Fisher test, p = 0.021). Conclusion Findings imply early alteration of the substantia nigra in XDP mutation carriers prone to develop parkinsonism. Thus, substantia-nigra hyperechogenicity may be regarded as a preclinical risk marker of parkinsonism-predominant XDP. Furthermore, this biomarker is clustered in some families suggesting the existence of one or more genetic co-factors influencing the phenotype of the disease.

Spasticity is a functionally limiting disorder that commonly occurs following stroke or severe brain injury, and may lead to disability and pain. In tandem with neurorehabilitation, botulinum toxin type A (BoNT-A) is the recommended first-line treatment for spasticity and, to date, the majority of trials have reported BoNT-A use in patients >6months after ictus. The present meta-analysis aimed to evaluate the effects of early BoNT-A injection for post-stroke spasticity on improvements in hypertonicity, disability, function and associated pain. A literature search yielded six studies reporting the effects of BoNT-A treatment within 3months post-stroke; three in the upper limb and three in the lower limb. All six studies permitted concomitant rehabilitation. Reduction in hypertonicity was compared in all six studies and revealed a significant treatment effect (P=0.0002) on the most affected joints between weeks 4 and 12 following injection. However, no significant effects of treatment were observed for improvement in disability at week 4 or improvement in function at weeks 4 and 20-24. A trend towards reduction in spasticity-related pain at week 4 following BoNT-A treatment (P=0.13) was also observed. These results demonstrate the beneficial effects of BoNT-A treatment on improving hypertonicity within 3months post-stroke and emphasise the importance of concomitant neurorehabilitation therapy.

Highlights • X-linked dystonia parkinsonism is linked with non-motor symptoms and changes in ADL. • Hiligaynon is the mostly used language in the Panay Islands, where XDP is endemic. • Validation of Parts IIIB and IV of XDP–MDSP scale to the native languages was done. • Filipino and Hiligaynon versions of the scale are internally valid and reliable., Introduction X-linked dystonia-parkinsonism (XDP) is a progressive movement disorder which also encompasses non-motor features and alterations in activities of daily living. The study aims to translate the Parts IIIB (Non-Motor Features) and IV (Activities of Daily Living) of the XDP-Movement Disorder Society of Philippines Rating Scale to Filipino and Hiligaynon and subsequently validate these versions, which are more understandable to the natives given that XDP originated from the Panay Islands in the Philippines. Methods This is a cross-cultural, cross-sectional validation study, composed of the following steps: forward translation, backward translation, panel reconciliation, pretesting, and field testing. Two sets of 10 XDP patients were recruited to the Filipino and Hiligaynon groups for pretesting and cognitive debriefing while another 2 sets of 50 XDP patients were assigned for field testing. Results The Filipino version had a good internal consistency with a Cronbach’s alpha of 0.951 during the pretesting and 0.886 during the field testing. Similar results were seen in the Hiligaynon version (0.837; 0.900). Both also had good conceptual equivalence as demonstrated by significant Pearson r values of 0.384 to 0.814 for the Filipino and 0.355 to 0.800 for the Hiligaynon versions. Conclusion The Filipino and Hiligaynon versions of the Parts IIIB and IV of the XDP–MDSP scale are internally valid and reliable. These scales are considered acceptable to assess the severity of the non-motor features and difficulties in activities of daily living among XDP patients.

SummaryGenerating tier 2 HIV-neutralizing antibody (nAb) responses by immunization remains a challenging problem, and the immunological barriers to induction of such responses with Env immunogens remain unclear. Here, some rhesus monkeys developed autologous tier 2 nAbs upon HIV Env trimer immunization (SOSIP.v5.2) whereas others did not. This was not because HIV Env trimers were immunologically silent because all monkeys made similar ELISA-binding antibody responses; the key difference was nAb versus non-nAb responses. We explored the immunological barriers to HIV nAb responses by combining a suite of techniques, including longitudinal lymph node fine needle aspirates. Unexpectedly, nAb development best correlated with booster immunization GC B cell magnitude and Tfh characteristics of the Env-specific CD4 T cells. Notably, these factors distinguished between successful and unsuccessful antibody responses because GC B cell frequencies and stoichiometry to GC Tfh cells correlated with nAb development, but did not correlate with total Env Ab binding titers.

X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset basal ganglia model disease associated with severe striatal atrophy. Anatomical changes exceeding striatal pathology were not yet described in XDP. The present study aimed to assess the microstructure of white matter tracts in XDP using magnetic resonance tomography.Diffusion-weighted imaging was done in 10 XDP patients, aged 42.2 years (SD 8.1), and 14 ethnicity and age-matched controls, aged 40.2 years (SD 6.4). Based on diffusion tensor images, mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated.Except for in the occipital lobe, XDP patients showed generally increased MD values across the entire white matter. FA map analysis identified four significant clusters with controls showing higher FA values than XDP patients. Involved regions included the fornix, anterior thalamic radiation, corticospinal tract, and superior corona radiata bilaterally. In the fornix and the anterior thalamic radiation, the UPDRSIII total score showed a negative correlation with mean FA values at a trend level (tau = -0.40, p = 0.053). Volumetric analysis revealed significant gray matter volume loss of putamen (F(1,19) = 44.2, p 0.001), caudate nucleus (F(1,19) = 54.3, p 0.001), and pallidum (F(1,19) = 8.9, p = 0.007).The present study confirms striatal atrophy in XDP and provides evidence for a strong involvement of the white matter and the pallidum. This calls into question the previously held concept of exclusive striatal atrophy in this unique movement disorder. The spared occipital region may point towards a lack of anatomical connections with the atrophied striatum.

Objective Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. Methods Five male Filipino patients (mean age 42.4, range 34–52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30 min and during 25/30 min of high-frequency GPi stimulation. Results While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231 ± 102% in comparison to baseline values), a decrease was observed in the GPe (22 ± 10%). Extracellular glutamate levels largely remained unchanged. Conclusions Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs.

Background Whether patients suffering from acute ischemic stroke and undergoing endovascular recanalization should be treated under general anesthesia (GA) or conscious sedation (CS) is a matter of debate. According to retrospective studies, GA appears to be associated with a worse outcome than CS. The underlying mechanisms are unknown, but hypotension and hypocapnia during GA have been suggested. There are no prospective data on this question. Methods We prospectively analyzed consecutive patients who were treated with endovascular recanalization from 11, 2013 to 03, 2014 regarding blood pressure, end-tidal carbon dioxide (etCO 2 ), cerebral oximetry (by near-infrared spectroscopy), ventilation parameters, response to commands, basic parameters (age, gender, percentage of posterior circulation stroke, National Institutes of Health Stroke Scale score [NIHSSS] on admission, NIHSSS at discharge, rate of successful recanalization [thrombolysis in cerebral infarction scale >2a], duration of intervention, symptom-to-recanalization time, and door-to-needle time), and medication used. Results Forty-four patients (29 under GA and 15 in CS) were included. Significant differences between the groups (GA versus CS) were found in the median dose of norepinephrine (.4 mg/hour versus .1 mg/hour, P = .003), mean systolic blood pressure (139.67 mm Hg versus 155.00 mm Hg, P = .003), mean duration of relative hypotension (systolic blood pressure P = .004), and mean etCO 2 values (37.29 mm Hg versus 27.33 mm Hg, P = .004). Conclusions In this small prospective study, patients under CS required less vasopressor medication and had a higher mean blood pressure than those under GA, but they also showed signs of hyperventilation. The impact of these physiological differences on outcome needs to be studied in randomized trials.

We carry out probabilistic phase-space sampling of mesoscopic Schrodinger cat quantum states, demonstrating multipartite Bell violations for up to 60 qubits. We use states similar to those generated in photonic and ion-trap experiments. These results show that mesoscopic quantum superpositions are directly accessible to probabilistic sampling, and we analyze the properties of sampling errors. We also demonstrate dynamical simulation of super-decoherence in ion traps. Our computer simulations can be either exponentially faster or slower than experiment, depending on the correlations measured.

More than a third of stroke patients will develop post-stroke spasticity, especially involving the paretic upper limbs. Despite established, intensive rehabilitation programmes in place, spasticity may still affect a post-stroke patient's quality of life and create economic and caregiver burdens. Hence, there is a need to explore how botulinum toxin (BTX) therapy may further improve patient outcomes. Consensus guidelines on the clinical use of BTX for established and symptomatic upper-limb spasticity are now available. While BTX therapy has been universally shown to reduce muscle tone in spasticity, its corresponding improvement in functional-outcome measures are far from consistent. This review article attempts to analyse the reasons for the inconsistency and makes the case that improved and reliable functional outcomes after BTX therapy may be achieved when: patient-specific goals that incorporate realistic expectations (such as improving passive as well as active functions and reducing pain) are used as functional-outcome measures; patients are followed up over a reasonable amount of time so as to optimise learning, rehabilitation and possibly even allow plasticity to occur; and, correct and thoughtful muscle targeting that considers various factors, such as spread, technique and avoidance of compensatory muscles, is employed. This article also summarises the characteristics of post-stroke patients who are at greatest risk for developing spasticity and those who are most likely to become the "best responders;" and, it attempts to outline the potential advantages of early BTX therapy in the acute to sub-acute post-stroke period, while spasticity is still evolving.

Introduction/Background Initial muscle tone increase may be apparent within 6 weeks, and even days, post-stroke. Botulinum toxin-A (BoNT-A), an effective and well-tolerated treatment for upper limb spasticity (ULS), improves muscle tone and function, however most studies were conducted > 6 months post-stroke. The ONTIME and ABCDE-S studies assessed efficacy and safety of early use (2–12 weeks post-stroke) of abobotulinumtoxinA (aboBoNT-A) in ULS. Material and method ABCDE-S ( NCT00234546 ; 2008): 24-week, randomised (1:1 aboBoNT-A [n = 80]: placebo [n = 83]), study assessing muscle tone changes in patients treated within 2–12 weeks of first stroke, with a Modified Ashworth Scale (MAS) score ≥ 1+. ONTIME ( NCT02321436 ; 2016): 28-week, randomised study (2:1 aboBoNT-A [n = 28]: placebo [n = 14]), assessing time to appearance or reappearance of reinjection criteria in patients with MAS score ≥ 2 treated 2–12 weeks post-stroke. All observed or volunteered adverse events (AEs) were recorded. Results MAS score improvements at Week 4 were greater in aboBoNT-A-treated patients than placebo in both studies (ABCDE-S −1.5 vs. −0.5; ONTIME −1.25 vs. −0.25). At 12-weeks post-injection, fewer aboBoNT-A-treated patients versus placebo had MAS scores ≥ 2 in ONTIME (29.6 vs. 69.2%) and ABCDE (21.3 vs. 60.2%) ( Table 1 ). In ONTIME, 11 (39.3%) aboBoNT-A-treated patients did not require reinjection for ≥ 28 weeks versus 2 (14.3%) for placebo. AboBoNT-A was well-tolerated; most AEs were mild–moderate in intensity, with no clinically significant differences in AEs between groups ( Table 2 ). Six patients had treatment-related AEs: two in placebo groups (dysuria and complex regional pain syndrome), and four in aboBoNT-A groups (fatigue [n = 2], pyrexia, muscular weakness). No serious AEs or deaths were considered treatment-related. Conclusion Early treatment with aboBoNT-A (2–12 weeks) was well-tolerated and had a longer time to reinjection versus placebo.

Rare earth elements (REE) analysis was carried out in two coral species Diploria strigosa and Copophyllia natans from Isla de Sacrificios Reef (ISR) (19° 10′ 51.6″N; 96° 5′ 45.6″W) Veracruz, Mexico. Both corals were cut at the top, middle and bottom parts to detect possible differences in REE concentrations related to water masses and sediment inputs. An enrichment in heavy rare elements (HREE) compared to light rare elements (LREE) at the top of Diploria strigosa and Copophyllia natans, evidenced by (La/Lu)SN

Follicular helper T cells (Tfh cells) are a CD4 T cell subset essential for germinal center formation and B cell responses, although their role in allergy and allergen-specific immunotherapy (AIT) is unclear. Here, we show that AIT-treated patients have a higher ratio of regulatory Tfh cells (Tfr) to follicular T cells (Tfh) and hypothesize an IL-2 dependent mechanism.

X-linked Dystonia-Parkinsonism (XDP) is a Mendelian neurodegenerative disease that is endemic to the Philippines and is associated with a founder haplotype. We integrated multiple genome and transcriptome assembly technologies to narrow the causal mutation to the TAF1 locus, which included a SINE-VNTR-Alu (SVA) retrotransposition into intron 32 of the gene. Transcriptome analyses identified decreased expression of the canonical cTAF1 transcript among XDP probands, and de novo assembly across multiple pluripotent stem-cell-derived neuronal lineages discovered aberrant TAF1 transcription that involved alternative splicing and intron retention (IR) in proximity to the SVA that was anti-correlated with overall TAF1 expression. CRISPR/Cas9 excision of the SVA rescued this XDP-specific transcriptional signature and normalized TAF1 expression in probands. These data suggest an SVA-mediated aberrant transcriptional mechanism associated with XDP and may provide a roadmap for layered technologies and integrated assembly-based analyses for other unsolved Mendelian disorders.

Objective To determine the prevalence of and the factors associated with tardive dyskinesia (TD) among Filipino patients with schizophrenia admitted at the National Center for Mental Health. Study Design Cross-sectional study. Methods A total of 227 inpatients fulfilling the DSM-IV TR criteria for schizophrenia participated in the study. Demographic data including age, disease duration and medication intake were obtained. The Abnormal Involuntary Movement Scale (AIMS) and Simpson Angus Rating Scale (SARS) were performed on all patients. Odds of developing TD in relation to the different variables were computed. The association between study variables and development of TD was also evaluated using the Chi-square test. Findings Our cohort of patients had a mean age of 40 (range: 19–73 years old), had a mean disease duration of 6 years, had a daily neuroleptic dose of 700 mg in chlorpromazine equivalent, and had a lifetime neuroleptic exposure of at least 5 years. The prevalence rate of TD was 20.3% (46 out of 227 patients). Fifty-three percent of patients had significant extrapyramidal features (SARS ≥3). TD was noted more in females and older age groups. The other factors associated with TD : were those patients with longer duration of illness and those patients with longer cumulative exposure to neuroleptic drugs. There was no association found with regard to the presence of diabetes mellitus type II, to the use of anticholinergic drugs, to the history of substance abuse and to the history of electroconvulsive therapy. Conclusions Despite the predominant use of first-generation antipsychotic agents, the prevalence of TD among Filipino schizophrenic patients is similar to that reported among Asians, but lower than that reported among our Western counterparts. The results may be affected by differences in methodological, racial and genetic determinants.

A numerical investigation has been performed for the time-dependent motion of a constant property, Newtonian fluid in a counter-current shearing flows configuration. In the geometry of interest, two initially separated streams are made to flow counter to each other at bulk average velocities U 1 and U 2 along the streamwise ( x -coordinate) direction through a pair of stacked, straight, parallel channels. The channels have width W , height H /2 and length L , and are separated by a pair of thin plates with a discontinuity in length L m centered at L /2. The counter-flowing streams interact dynamically in the space shared by the two channels, defined by the discontinuity between plates. This problem consists of a very simple Cartesian geometry with well posed initial and boundary conditions and yet, for the conditions explored, the resulting physics is highly non-linear and complex. Starting from rest, the counter-flowing streams in the shared space region initially display the characteristics of a two-dimensional saddle point flow when observed along the spanwise ( z -coordinate) direction. Soon thereafter, depending on the shapes of the velocity profiles imposed at the channel inlet planes and the respective Reynolds numbers of the opposing streams Re 1 , 2 ≡ U 1 , 2 H / 2 ν , two pairs of vortices aligned in the transverse ( y -coordinate) direction appear that can be stable or unstable. If the inlet plane velocity profiles are symmetric and Re 1 = Re 2 = 300 or Re 1 = 2 × Re 2 = 300 each of the two channel vortex pairs counter-rotates and they are stable over long periods of time. If, however, the inlet velocity profiles are anti-symmetric one pair of anti-symmetric co-rotating vortices dominates the flow and they orbit around each other. For this case, if Re 1 = Re 2 Re 1 = Re 2 > 200, in the presence of stretching by the background saddle point flow the merging of the vortex pair is unstable and the resulting vortex structure ultimately collapses in a temporary burst of complex, three-dimensional, unsteady motion. Soon thereafter, the formation, merging and collapse of this vortex pair repeats. Aside from their intrinsic fundamental interest, the phenomena observed have potential applications for the controlled mixing of fluid streams at both low and high Reynolds numbers. Flow visualization results show how this can be achieved in a device consisting of a number of basic counter-current flow units concatenated in series.

A new formulation to easy simulation and optimization of gas and oil production systems is presented in this work. The problem of interest corresponds to the typical daily gas and oil production calculation, i.e. a one-day time period planning. The simulation problem considers determination of oil and gas production for the current topology. The optimization problem is established by considering that the instantaneous production of the gas/oil network must optimally satisfy a given demand. Non-linear behavior and reverse flow is assumed for wells and cubic equations of state are used to estimate thermodynamic properties. The resulting model contains differential and algebraic equations for a given fixed topology of interconnected wells coupled with surface pipeline networks. The model combines DASSL to solve the inner set of differential–algebraic equations, and Knitro to solve both the optimization problem and the overall set of non-linear equations. The good performance of the model and the numerical strategy is illustrated with real cases of study.

We have previously shown evidence for the existence of a calcium-independent, GTP-regulated mechanism of secretion from neutrophils, but this secretory mechanism remains to be fully elucidated. Cyclin-dependent kinase 5 (Cdk5), the various substrates of which include Munc18 and synapsin 1, has been implicated in neuronal secretion. Although the Cdk5 activator, p35, and Cdk5-p35 activity are primarily associated with neurons, we report here that p35 also exists in neutrophils and that an active Cdk5-p35 complex is present in these cells. Cdk5-p35 activity in human neutrophils is mostly localized in secretory granules, which show an increase in Cdk5-p35 level and activity upon GTP stimulation. The potent Cdk5 inhibitor, roscovitine, completely blocks GTP-stimulated granule Cdk5 activity, which accompanies lactoferrin secretion from neutrophil-specific granules. Roscovitine also inhibits GTP-induced lactoferrin secretion and surface localization of the secretion markers, CD63 and CD66b, to a certain extent. Furthermore, neutrophils from wild-type mice treated with roscovitine and neutrophils from p35(-/-) mice exhibit comparable surface expression levels of both CD63 and CD66b upon GTP stimulation. Although our data suggest that other molecules control GTP-induced secretion from neutrophils, it is clear that Cdk5-p35 is required to elicit the maximum GTP-induced secretory response. Our observation that multiple proteins in neutrophil granules serve as specific substrates of Cdk5 further supports the premise that the kinase is a key component of the GTP-regulated secretory apparatus in neutrophils.

Cdk5 is ubiquitously expressed in all tissues, but its activators, p35 and p39, are principally found in brain, and Cdk5 activity has mostly been associated with brain development, particularly neuronal differentiation and migration. Here we show that the p35 transcript and protein are also present in the testis, and an active Cdk5.p35 complex exists in this tissue as well. Cdk5 and p35 are prominently observed in elongating spermatid tails, particularly over the tail outer dense fibers (ODF). The appearance of Cdk5.p35 proceeds from the proximal to the distal end of elongating spermatids, coinciding with the proximal to distal assembly of ODF along the length of the tail axoneme. Incidentally, increased Cdk5.p35 activity is observed in isolated elongating spermatids and at a time when elongating spermatids appear in the developing testis, suggesting a role for Cdk5.p35 in spermiogenesis. The presence of Cdk5 and p35 in ODF isolated from rat sperm tails implies a strong association among these proteins. In vitro ODF phosphorylation by Cdk5.p35 and decreased in vivo sperm tail ODF phosphorylation in p35-deficient mice indicate that Cdk5.p35 is an integral component of ODF and that ODF is a functional Cdk5.p35 target in the testis. Our results demonstrate for the first time that Cdk5.p35 may participate in the regulation of sperm tail development via a mechanism involving ODF phosphorylation. Apparently, as in brain development, Cdk5.p35 plays a part in testis development.

La ecuacion de Starling continua siendo la clave para comprender el intercambio de liquidos a traves de la membrana endotelial, pero factores como la superficie vascular perfundida y, en menor grado, el drenaje linfatico pueden desempenar un papel importante en la filtracion transcapilar de fluidos. Asimismo, se han identificado mecanismos activos que actuarian fundamentalmente sobre las proteinas y que justificarian comportamientos que no se rigen por la citada ecuacion de Starling Los avances mas significativos se han experimentado en el conocimiento de los mecanismos de reabsorcion y aclaramiento del edema pulmonar. En primer lugar, un hecho de extraordinaria relevancia fue la descripcion, en la decada de los ochenta, de mecanismos de transporte activo de Na a traves de la membrana alveolar. El epitelio alveolar transporta iones Na de forma activa y el agua sigue pasivamente los cambios osmoticos originados por este bombeo de iones. Asimismo, el descubrimiento de canales especificos para el transporte transalveolar de agua no ligado al movimiento de iones constituye un hecho de extraordinaria relevancia. Estos canales estan constituidos por proteinas presentes en la membrana alveolar y su descubrimiento abre un campo realmente apasionante ante las posibilidades de intervencion Finalmente, cada vez parece mas evidente que el papel del drenaje linfatico es inferior al que clasicamente se le ha otorgado, de forma que su contribucion al aclaramiento del edema pulmonar no pasaria de un 10-15%

Ten provenance/progeny tests of Bombacopsis quinata were established in Venezuela and Colombia using open-pollinated (OP) seed collected from throughout its natural range. In addition, two full-sib progeny tests were established in Colombia with seed from crosses made in a second-generation seed orchard. Average survival of all tests was approximately 80%, with the local source from Colombia (Atlantico) having slightly better survival in Colombia. Average growth rates at age 8 years were 6–7 m height and 12–13 cm DBH. Provenance×country interaction was highly significant between Colombia and Venezuela, although at a within-provenance level, families performed relatively consistently in the two countries (rBg=0.58). There was no important genotype×environment interaction at the provenance or family level between test sites in the same country. There were large provenance effects in both countries. In Colombia, two provenances from Nicaragua (Hacienda San Juan and Los Playones) performed as well as the local source, with 11–16% more volume than average. In Venezuela, provenances originating in areas of 1600–2100 mm of annual rainfall (Choluteca, Honduras, and Guanacaste, Costa Rica) had volumes 26% above average, while the local source performed poorly both in survival and growth. Heritabilities for growth traits are moderate and increase with age up to 0.25–0.30 at age 8 years. Dominance variance is relatively unimportant as it is approximately 1 4 or less than the size of additive variance. After the appropriate provenances have been identified, additional genetic gains of up to 50% in volume are possible from family and within family selection.

Objective To determine whether early post-stroke (within 12 weeks) abobotulinumtoxinA (aboBoNT-A; Dysport ® ) injections delay the appearance or progression of upper limb symptomatic spasticity. Prevalence and severity of spasticity continues to increase during the first year after stroke. However, muscle tone changes in the affected limb may be apparent within 2 weeks of stroke. AboBoNT-A is a recognized effective focal intervention for reducing upper limb spasticity, but is usually administered ≥ 3 months post-stroke. There are limited data regarding whether early treatment with botulinum toxin A delays development of symptomatic post-stroke spasticity. Material/Patients and methods The ONTIME pilot study was a 28-week, phase IV, randomized (2:1, aboBoNT-A 500U:placebo), double-blind study to assess the impact of aboBoNT-A intramuscular injections administered within 2–12 weeks post-stroke on appearance or reappearance of symptomatic spasticity in patients with Modified Ashworth Scale (MAS; muscle tone) score ≥ 2 at baseline. Primary endpoint was time between first injection and visit when composite reinjection criteria were met. Reinjection criterion was a novel composite index, defined as a MAS score ≥ 2 and one of the following signs of symptomatic (disabling) spasticity: pain, involuntary movements, impaired active or passive function. Results Forty-two patients (28 aboBoNT-A, 14 placebo; 78.6% male; mean [SD] age, 59.8 [12.3] years; MAS ≥ 2) from Malaysia, Philippines, Singapore and Thailand were randomized and injected; 76.2% had symptomatic spasticity and median [range] time since stroke was 5.86 [2.3–11.7] weeks. In most patients (73.8%), elbow flexors were selected as the primary target muscle group. Median [95% CI] time to reaching reinjection criteria was 156.0 [86.0–206.0] days for aboBoNT-A and 32.0 [29.0–114.0] days for placebo ( P = 0.0176). Discussion/Conclusion Median time between first injection (administered in patients 2–12 weeks post-stroke, MAS ≥ 2) and appearance of reinjection criteria (signs of symptomatic spasticity) was statistically significantly longer with aboBoNT-A compared with placebo. Safety profile was consistent with the known profile of aboBoNT-A.

Objective Prevalence and severity of spasticity continues to increase in the first year after stroke. Botulinum toxin A (BoNT-A) is an effective focal intervention for reducing upper limb spasticity and is usually administered ≥ 3 month after stroke since this is considered to be the time when clinical signs of increased muscle tone/spasticity symptoms are likely to become established. However, muscle tone changes in the affected limb may already be apparent within 2 weeks post-stroke and there is limited data on whether early treatment with BoNT-A may delay development of disabling (symptomatic) spasticity. Material/Patients and methods The ONTIME pilot study was a 28-week, phase IV, randomized (2:1; abobotulinumtoxinA [Dysport ® , aboBoNT-A]: placebo), double-blind, placebo-controlled, exploratory trial to assess the impact of aboBoNT-A injections administered within 2–12 weeks after stroke. The primary endpoint was the time between the 1st study injection and the visit when reinjection criteria were met. Reinjection criteria were defined as MAS (muscle tone) increased to ≥ 2 and appearance or reappearance of one of the following signs of symptomatic spasticity: pain, involuntary movements, impaired active or passive function. Results Forty-two patients (28 aboBoNT-A, 14 placebo) from Malaysia, Philippines, Singapore and Thailand were randomised. Mean [SD] age was 59.8 [12.3] years, 79% male, 32 patients (76%) had symptomatic spasticity and mean [SD] time since stroke was 6.29 [2.73] weeks. In the majority of cases (74%), the elbow flexors were selected as the primary target muscle group, followed by wrist flexors (14%) and finger flexors (2%). Discussion/Conclusion Symptomatic spasticity was present in the majority of cases (76%) 6 weeks after stroke. This indicates that current standard clinical practice in terms of time to start spasticity treatment with BoNT-A (≥ 3 month after stroke) may not be optimal. The ONTIME pilot study will investigate the impact of early post-stroke treatment with aboBoNT-A.

A numerical investigation was conducted to analyze the unsteady flow-field and heat-transfer characteristics for a tandem pair of square cylinders in a laminar channel flow. The drag, lift, and heat transfer coefficients from the downstream heated cylinder due to inline and offset eddy-promoting cylinders were studied. The results show that the drag coefficient and cylinder Nusselt number decrease as the heated cylinder approaches the wall. The highest Strouhal number value is observed in the channel-centered, inline-eddy configuration. Complex periodic vortex shedding develops when the eddy promoter is offset from the primary cylinder.

Introduction and Objectives: A total of 456 patients were recruited globally for the ULIS II study. To compare the data from South Asia (SA) with the global (GLB) results, a subanalysis was performed.Methods: A total of 51 patients from Hong Kong, Philippines, Thailand, Taiwan, Malaysia, and Singapo

Annexin proteins specifically bind anionic phospholipids such as phosphatidylserine, which are normally confined to the cytoplasmic leaflet of cellular membranes. During programmed cell death, or apoptosis, this phospholipid asymmetry is lost, and anionic phospholipids are exposed on the extracellular leaflet of the plasma membrane where they are accessible to exogenously added, labeled annexins. Chemically [e.g., fluoroscein isothiocyanate (FITC)]-modified annexin V has been widely used to detect and enumerate apoptotic cells by flow cytometry. We prepared chimeric proteins containing green fluorescent protein (GFP) fused to annexin V. A chimera containing GFP fused to the C-terminus of annexin V was soluble and fluorescent, but was unable to bind phospholipids. In contrast, a chimera containing GFP fused to the N-terminus of annexin V specifically bound apoptotic cells. GFP–annexin V represents a sensitive and facile alternative to FITC–annexin V for studies of apoptosis.

Two exorreic basins from southern Mexico were studied in order to estimate sand composition and provenance in tropical latitudes based on sample suites collected under similar climate conditions and relief but with differences in parent rock type. The climate in these basins is warm to humid and the topography reflects young basins which belong to an active margin. The westward basin, La Tigra, has a greater outcrop area of plutonic rocks, whereas the Petatlan Basin is characterized by a greater abundance of metamorphic rocks. Chemical analysis of sediment samples show greater weathering in Petalan than in La Tigra Basin. Microprobe analysis of detrital magnetite grains from both basins yield evidence of a felsic plutonic/volcanic or metamorphosed mafic or ultramafic source. The average mineralogical maturity index ( Mi = Q F + RF ) is very similar for both basins (0.30 in La Tigra and 0.35 in Petatlan), while the provenance index (Pi = F RF ) shows average values of 0.46 for La Tigra Basin and 0.22 for Petatlan Basin. These differences seem to be mainly related to lithologic differences. Beach sand samples reflect a lithological admixture of sand derived from both basins, based on chemical analysis and on provenance index (0.34).