Diagnostic value of cerebral vasospasm by transcranial doppler ultrasound in Vietnamese patients with subarachnoid hemorrhage.

OBJECTIVE: Although the application of transcranial Doppler (TCD) ultrasonography in clinical diagnosis of cerebral vasospasm is popular in clinical practice in Vietnam, available evidence of the predictive value of vasospasm on TCD in the literature was mostly reported from large institutions in developed countries. Hence, this study was conducted to evaluate the value of TCD ultrasonography in the diagnosis of vasospasm in patients with subarachnoid hemorrhage (SAH) in Vietnam. PATIENTS AND METHODS: This is a prospective observational study of all aneurysmal SAH patients consecutively admitted to a single center between 2008 and December 2011. TCD and 64-slice computed tomographic angiography (CTA) were used to cerebral vasospasm in SAH patients. RESULTS: 316 patients were analyzed (mean age = 52.97±12.27 years, 52.2% males). There were statistically significant difference rates of the cerebral vasospasm by Hunt and Hess Classification and Fisher classification (p <0.01). The proportion of the patients with cerebral vasospasm who were diagnosed exactly by TCD was 95.2%, while the proportion of the patients without cerebral vasospasm diagnosed exactly was 91.5%. TCD predictive diagnostic value was the highest, with the sensitivity of 0.95 (95% CI: 0.91-0.98), specificity of 0.91 (95% CI: 0.85-0.96), positive predictive value of 0.94 (5% CI: 0.90-0.97) and negative predictive value of 0.93 (95 CI: 0.87-0.97). Hemiplegia was the clinical symptom with the highest diagnostic value with the sensitivity of 0.34 (95% CI: 0.27-0.41), specificity of 0.92 (95% CI: 0.86-0.96), positive predictive value of 0.86 (95% CI: 0.76-0.93) and negative predictive value of 0.49 (95% CI: 0.41-0.54). CONCLUSIONS: Evidence of vasospasm diagnosis on TCD ultrasonography was found with high accuracy. Current study enables to suggest the wide application of TCD in Vietnam health facilities from central to grassroots levels instead of the CTA use.

Occurrence of Taenia species in pigs in slaughterhouses in Phu Tho province, northern Vietnam.

Pigs act as the intermediate hosts of the zoonotic tapeworms Taenia solium and Taenia asiatica, as well as of the non-zoonotic Taenia hydatigena. In Vietnam, human taeniasis and cysticercosis have been reported throughout the country; however, data on porcine cysticercosis are scarce. Our study aimed to estimate the prevalence of Taenia spp. in slaughtered pigs in two districts in Phu Tho, a mountainous province in northern Vietnam from where neurocysticercosis patients commonly originate. The carcasses of 399 pigs from 51 small-scale abattoirs were checked for cysticerci, while tongue, liver, masseter muscles, diaphragm and heart were sliced and examined. Retrieved cysticerci underwent polymerase chain reaction-restriction fragment length polymorphism and sequencing for species confirmation. Blood was also collected to detect antibodies by lentil lectin-purified glycoprotein enzyme-linked immunoelectrotransfer blot (LLGP-EITB) and recombinant T24H antigen (rT24H)-EITB and circulating antigens by B158/B60 Ag-ELISA. In two pigs, T. asiatica cysticerci were found, confirming the presence of the parasite in pigs in Vietnam at a low prevalence (0.5%; 95% exact confidence interval (CI): 0-1.19%). Cysticerci of T. solium were found in none of the pigs, although one serum sample was positive for antibodies in both LLGP-EITB and rT24H-EITB. Furthermore, a high prevalence of T. hydatigena cysticercosis was observed (18.0%; 95% Wilson score CI: 14.6-22.1%). In more than half of the T. hydatigena-positive pigs, circulating antigens were detected by Ag-ELISA, confirming that this test cannot be used to diagnose T. solium cysticercosis in this region. Finally, Spirometra erinaceieuropaei was found in one pig liver. It is the first record of this zoonotic cestode species in pigs in Vietnam. Overall, the findings confirmed the complex epidemiology of Taenia spp. in pigs in Vietnam.

Real-time Subject-specific Head and Facial Mimic Animation System using a Contactless Kinect Sensor and System of Systems Approach.

Facial palsies due to stroke, accidental and sportive injuries or sometimes without etiology, affect the professional and personal lives of involved patients. These disorders are not only a functional handicap but also a social integration impairment. The recovery of facial mimics with a normal and symmetrical facial expression allows involved patients to improve their living conditions and social identity. Current approaches lack of visual feedbacks. To monitor facial mimics and head movements in a quantitative and objective manners, a computer-aided animation system needs to be developed. Numerous systems have been proposed using single camera, stereo camera, 3-D scanner, and Kinect approaches. In particular, Kinect contactless sensor has been proven to be very suitable for 3-D facial simulation applications. However, little studies have employed the Kinect sensor for real-time head animation applications. Consequently, this study developed a real-time head and facial mimic animation system using the contactless Kinect sensor and the system of systems approach. To evaluate the accuracy of the subject-specific Kinect-based geometrical models, magnetic resonance imaging (MRI) data were used. As results, the mean distance deviation between generated Kinect-based and reconstructed MRI-based geometrical head models are approximately 1 mm for two tested subjects. The generation times are 9.7 s ± 0.3 and 0.046 s ± 0.005 by using the full facial landmarks and MPEG-4 facial landmarks respectively. Real-time head and facial mimic animations were illustrated. Particularly, the system could be executed at a very high framerate (60 fps). Further developments relate to the integration of texture information and internal structures such as a skull and muscle network to develop a full subject specific head and facial mimic animation system for facial mimic rehabilitation.

Association between in-hospital guideline adherence and postdischarge major adverse outcomes of patients with acute coronary syndrome in Vietnam: a prospective cohort study.

OBJECTIVE: We aimed to determine the association between physician adherence to prescribing guideline-recommended medications during hospitalisation and 6-month major adverse outcomes of patients with acute coronary syndrome in Vietnam. DESIGN: Prospective cohort study. SETTING: The study was carried out in two public hospitals in Vietnam between January and October 2015. Patients were followed for 6 months after discharge. PARTICIPANTS: Patients who survived during hospitalisation with a discharge diagnosis of acute coronary syndrome and who were eligible for receiving at least one of the four guideline-recommended medications. EXPOSURES: Guideline adherence was defined as prescribing all guideline-recommended medications at both hospital admission and discharge for eligible patients. Medications were antiplatelet agents, beta-blockers, ACE inhibitors or angiotensin II receptor blockers and statins. MAIN OUTCOME MEASURE: Six-month major adverse outcomes were defined as all-cause mortality or hospital readmission due to cardiovascular causes occurring during 6 months after discharge. Cox regression models were used to estimate the association between guideline adherence and 6-month major adverse outcomes. RESULTS: Overall, 512 patients were included. Of those, there were 242 patients (47.3%) in the guideline adherence group and 270 patients (52.3%) in the non-adherence group. The rate of 6-month major adverse outcomes was 30.5%. A 29% reduction in major adverse outcomes at 6 months after discharge was found for patients of the guideline adherence group compared with the non-adherence group (adjusted HR, 0.71; 95% CI, 0.51 to 0.98; p=0.039). Covariates significantly associated with the major adverse outcomes were percutaneous coronary intervention, prior heart failure and renal insufficiency. CONCLUSIONS: In-hospital guideline adherence was associated with a significant decrease in major adverse outcomes up to 6 months after discharge. It supports the need for improving adherence to guidelines in hospital practice in low-income and middle-income countries like Vietnam.

Long-term outcome in survivors of neonatal tetanus following specialist intensive care in Vietnam.

BACKGROUND: Neonatal tetanus continues to occur in many resource-limited settings but there are few data regarding long-term neurological outcome from the disease, especially in settings with critical care facilities. METHODS: We assessed long-term outcome following neonatal tetanus in infants treated in a pediatric intensive care unit in southern Vietnam. Neurological and neurodevelopmental testing was performed in 17 survivors of neonatal tetanus and 18 control children from the same communities using tools previously validated in Vietnamese children. RESULTS: The median age of children assessed was 36 months. Eight neonatal tetanus survivors and 9 community control cases aged < 42 months were tested using the Bayley III Scales of Infant and Toddler Development (Bayley III-VN) and 8 neonatal tetanus survivors and 9 community controls aged ≥42 months were tested using the Movement Assessment Battery for Children. No significant reductions in growth indices or neurodevelopmental scores were shown in survivors of neonatal tetanus compared to controls although there was a trend towards lower scores in neonatal tetanus survivors. Neurological examination was normal in all children except for two neonatal tetanus survivors with perceptive deafness and one child with mild gross motor abnormality. Neonatal tetanus survivors who had expienced severe disease (Ablett grade ≥ 3) had lower total Bayley III-VN scores than those with mild disease (15 (IQR 14-18) vs 24 (IQR 19-27), p = 0.05) with a significantly lower cognitive domain score (3 (IQR 2-6) severe disease vs 7 (IQR 7-8) mild disease, p = 0.02). CONCLUSIONS: Neonatal tetanus is associated with long-term sequelae in those with severe disease. In view of these findings, prevention of neonatal tetanus should remain a priority.

Estimation of accuracy of patient-specific musculoskeletal modelling: case study on a post polio residual paralysis subject.

For patients with patterns ranging out of anthropometric standard values, patient-specific musculoskeletal modelling becomes crucial for clinical diagnosis and follow-up. However, patient-specific modelling using imaging techniques and motion capture systems is mainly subject to experimental errors. The aim of this study was to quantify these experimental errors when performing a patient-specific musculoskeletal model. CT scan data were used to personalise the geometrical model and its inertial properties for a post polio residual paralysis subject. After having performed a gait-based experimental protocol, kinematics data were measured using a VICON motion capture system with six infrared cameras. The musculoskeletal model was computed using a direct/inverse algorithm (LifeMod software). A first source of errors was identified in the segmentation procedure in relation to the calculation of personalised inertial parameters. The second source of errors was subject related, as it depended on the reproducibility of performing the same type of gait. The impact of kinematics, kinetics and muscle forces resulting from the musculoskeletal modelling was quantified using relative errors and the absolute root mean square error. Concerning the segmentation procedure, we found that the kinematics results were not sensitive to the errors (relative error<1%). However, a strong influence was noted on the kinetics results (deviation up to 71%). Furthermore, the reproducibility error showed a significant influence (relative mean error varying from 5 to 30%). The present paper demonstrates that in patient-specific musculoskeletal modelling variations due to experimental errors derived from imaging techniques and motion capture need to be both identified and quantified. Therefore, the paper can be used as a guideline.

Chalcone synthase and its functions in plant resistance.

Chalcone synthase (CHS, EC 2.3.1.74) is a key enzyme of the flavonoid/isoflavonoid biosynthesis pathway. Besides being part of the plant developmental program the CHS gene expression is induced in plants under stress conditions such as UV light, bacterial or fungal infection. CHS expression causes accumulation of flavonoid and isoflavonoid phytoalexins and is involved in the salicylic acid defense pathway. This review will discuss CHS and its function in plant resistance.

Validation of an ultra-fast UPLC-UV method for the separation of antituberculosis tablets.

A simple method using ultra performance LC (UPLC) coupled with UV detection was developed and validated for the determination of antituberculosis drugs in combined dosage form, i. e. isoniazid (ISN), pyrazinamide (PYR) and rifampicin (RIF). Drugs were separated on a short column (2.1 mm x 50 mm) packed with 1.7 mum particles, using an elution gradient procedure. At 30 degrees C, less than 2 min was necessary for the complete separation of the three antituberculosis drugs, while the original USP method was performed in 15 min. Further improvements were obtained with the combination of UPLC and high temperature (up to 90 degrees C), namely HT-UPLC, which allows the application of higher mobile phase flow rates. Therefore, the separation of ISN, PYR and RIF was performed in less than 1 min. After validation (selectivity, trueness, precision and accuracy), both methods (UPLC and HT-UPLC) have proven suitable for the routine quality control analysis of antituberculosis drugs in combined dosage form. Additionally, a large number of samples per day can be analysed due to the short analysis times.

Method transfer for fast liquid chromatography in pharmaceutical analysis: application to short columns packed with small particle. Part II: gradient experiments.

Liquid chromatography (LC) is currently considered as the gold standard in pharmaceutical analysis. Today, there is an increasing need for fast and ultra-fast methods with good efficiency and resolution for achieving separations in a few minutes or even seconds. A previous article (i.e. method transfer for fast LC in pharmaceutical analysis. Part I: isocratic separation) described a simple methodology for performing a successful method transfer from conventional LC to fast and ultra-fast LC in isocratic mode. However, for performing complex separations, the gradient mode is often preferred. Thus, this article reports transfer rules for chromatographic separations in gradient mode. The methodology was applied for the impurity profiling of pharmaceutical compounds, following two strategies. A first approach, using short columns (20-50mm) packed with 3.5microm particles and optimized HPLC instrumentation (with reduced extra-column and dwell volumes), was applied for the separation of a pharmaceutical drug and eight related impurities. Special attention was paid to the dwell (gradient delay) volume, which causes the most detrimental effect for transferring a gradient method. Therefore, the dwell volume was simultaneously decreased with the column dead volume. Under optimal conditions, it was possible to reduce the analysis time by a factor of 10, with an acceptable loss in resolution since the column length reduction is less critical in gradient than isocratic mode. The second tested approach was Ultra Performance Liquid Chromatography (UPLC), where sub-2microm particles were used simultaneously with very high pressures (up to 1000bar). A complex pharmaceutical mixture containing 12 compounds was separated in only 1.5min allowing a reduction of the analysis time by a factor of 15 in comparison to a conventional method, with similar peak capacity.

High throughput liquid chromatography with sub-2 microm particles at high pressure and high temperature.

In this study, ultra performance liquid chromatography (UPLC) using pressures up to 1,000 bar and columns packed with sub-2 microm particles has been combined with high temperature mobile phase conditions (up to 90 degrees C). By using high temperature ultra performance liquid chromatography (HT-UPLC), it is possible to drastically decrease the analysis time without loss in efficiency. The stability and chromatographic behavior of sub-2 microm particles were evaluated at high temperature and high pressure. The chromatographic support remained stable after 500 injections (equivalent to 7,500 column volumes) and plate height curves demonstrated the capability of HT-UPLC to obtain fast separations. For example, a separation of nine doping agents was performed in less than 1 min with sub-2 microm particles at 90 degrees C. Furthermore, a shorter column (30 mm length) was used and allowed a separation of eight pharmaceutical compounds in only 40s.

Method transfer for fast liquid chromatography in pharmaceutical analysis: application to short columns packed with small particle. Part I: isocratic separation.

Liquid chromatography (LC) is considered to be the gold standard in pharmaceutical analysis. Today, there is a need for fast and ultra-fast methods with good efficiency and resolution for achieving separations in few minutes or even seconds. The present work describes a simple methodology for performing a successful method transfer from conventional LC to fast and ultra-fast LC. In order to carry out fast separations, short columns (20-50mm) packed with small particles (3.5 and 1.7 microm) were used and their chromatographic performance was compared to that of a conventional column (150 mm, 5 microm). For that purpose, an optimized LC system was employed to limit extra-column volumes which can have a dramatic impact on efficiency and resolution. This paper reports the fundamental equations used for transferring an isocratic chromatographic separation performed with a given column geometry and chemistry to a smaller column packed with similar or identical stationary phase, without influence on chromatographic performance. For this purpose, the flow rate and the injected volume need to be adapted. The effect of column length and particle size reduction on chromatographic resolution and analysis time was described for an isocratic separation. Using the method transfer equations, it is possible to predict the new conditions to be used, for fast and ultra-fast separations. In this work, ultra-fast separations were achieved thanks to a new generation of instrumentation (ultra performance liquid chromatography, UPLC) which uses simultaneously short column packed with sub-2 microm particles and ultra-high pressure (up to 1000 bar). This work demonstrates an analysis time reduction up to a factor 12, compared to a conventional LC separation, without affecting the quality of separation. Therefore, the complete resolution of a pharmaceutical formulation was achieved in only a few seconds.

Recent developments in liquid chromatography--impact on qualitative and quantitative performance.

In order to reduce the analysis time and maintain good efficiency in liquid chromatography (LC), several solutions are currently being investigated. The focus of this study was to compare, both qualitatively and quantitatively, the chromatographic performance of a conventional LC with selected approaches, namely monolithic supports, high temperature LC (up to 90 degrees C), and sub-2 microm particles combined with high pressure (up to 1000 bar). This comparison was achieved from a qualitative point of view with a special attention paid to the analysis of time reduction, efficiency improvement, and pressure constraint. For this purpose, the different approaches were discussed using Knox curves and other kinetic plots. It appeared that columns packed with sub-2 microm particles under high-pressure conditions (UPLC) were well adapted and this option represents an attractive alternative to conventional LC; however, the other alternative approaches should not be neglected. The quantitative evaluation of these techniques was performed on the basis of the validation of results of a pharmaceutical formulation (Rapidocaïne), following SFSTP 2003 guidelines. Fast-LC approaches demonstrated equivalent performance to conventional LC in terms of trueness, precision, and accuracy profile, with a significant time reduction (up to 8x) according to the selected methodology.

Fast analysis in liquid chromatography using small particle size and high pressure.

In order to enhance chromatographic performances in terms of efficiency and rapidity, LC has recently evolved in the development of short columns packed with small particles (sub-2 microm) working at high pressures (> 400 bar). This approach has been described 30 years ago according to the fundamental chromatographic equations. However, systems and columns compatible with such high pressures have been introduced in the market in 2004 only. Advantages of small particles working at high pressure will be discussed in terms of sensitivity, efficiency, resolution, and analysis time. Potential problems encountered with high pressure in terms of frictional heating and solvent compressibility will also be discussed even if systems working at a maximum pressure of 1000 bar are not influenced by these parameters and give reliable and reproducible results. Several applications will highlight the potential and interest of this new technology.

Chromatographic behaviour and comparison of column packed with sub-2 microm stationary phases in liquid chromatography.

In order to reduce the analysis time and maintain good efficiency in liquid chromatography, it is advisable to simultaneously decrease the column length and the particle size of the chromatographic support. Therefore, several manufacturers have developed and commercialized short columns filled with particles that have a diameter smaller than 2 microm. The focus of this work was to check the chromatographic performance of such columns and compare possibilities offered by sub-2 microm supports with conventional columns in terms of analysis time reduction and efficiency improvements. For this purpose, different parameters were discussed namely: separation impedance (E), Knox curves (h,v), and number of plates by time unit (N/t0). Kinetic plots were also drawn. It appeared that sub-2 microm supports were well adapted to improve chromatographic performance and to reduce the analysis time. Furthermore, it was also demonstrated that the best chromatographic performances were reached with high pressure systems (up to 1000 bar).

Practical constraints in the kinetic plot representation of chromatographic performance data: theory and application to experimental data.

It is demonstrated that the kinetic plot representation of experimental plate height data can also account for practical constraints on the column length, the peak width, the viscous heating, and the mobile-phase velocity without needing any iterative solution routine. This implies that the best possible kinetic performance to be expected from a given tested support under any possible set of practical optimization constraints can always be found using a directly responding calculation spreadsheet template. To show how the resulting constrained kinetic plots can be used as a powerful design and selection tool, the method has been applied to a series of plate height measurements performed on a number of different commercial columns for the same component (butyl-parabene) and mobile-phase composition. The method, for example, allows one to account for the fact that the advantageous solutions displayed by the silica monolith and 5 microm particle columns in the large plate number range of the free kinetic plot are no longer accessible if applying a maximal column length constraint of Lmax = 30 cm. In the plate number range that remains accessible, the investigated sub-2 mum particle columns in any case perform (at least for the presently considered parabene separation) better than the 3.5 mum particle columns or silica monolith, especially if considering the use of system pressures exceeding 400 bar. The constrained kinetic plot method can also be used to select the best-suited column length from an available product gamma to perform a separation with a preset number of plates. One of the optimization results that is obtained in this case is that sometimes a significant gain in analysis time can be obtained by selecting a longer column, yielding the desired plate number at a larger velocity than that for a shorter column.

Renal kallikrein excretion: role of ethnicity, gender, environment, and genetic risk of hypertension.

BACKGROUND AND OBJECTIVE: Alterations in renal kallikrein excretion are well-described in hypertension, and kallikrein excretion may predict risk of developing hypertension, but kallikrein excretion has not been directly compared across several ethnic strata, nor have the effects of ethnicity, gender, environment, and genetic risk of hypertension been simultaneously considered as determinants of kallikrein. METHODS: We investigated determinants of kallikrein excretion in a cross-section of n = 204 normotensive subjects stratified by ethnicity (119 Caucasian, 33 African-American, 52 Asian), gender (109 men, 95 women), environment (spontaneous electrolyte intake/excretion), and heredity (genetic risk (family history) of hypertension). Results were interpreted by analysis of variance (with Bonferroni post hoc comparison corrections), analysis of covariance, multiple linear regression, and maximum likelihood. RESULTS: Urinary kallikrein activity varied substantially (F = 5.30, P = 0.006) across the three ethnic groups, with African-American values approximately 50% lower than Caucasian (P = 0.005) or Asian (P = 0.02). Ethnicity and gender (T = 3.24, P = 0.001) had independent effects on kallikrein, with women excreting approximately 50% more kallikrein than men, regardless of ethnicity. Subjects at genetic risk of hypertension were over-represented (P = 0.048) in the lower stratum of a bimodal distribution of kallikrein excretion (chi-square = 29.6, P < 0.001). Potassium excretion was diminished in African-Americans (P < 0.001 to P = 0.002), and in a multivariate analysis, potassium excretion was the strongest correlate of kallikrein excretion (T = 4.10, P = 0.0001). In a subset of Caucasian and African-American individuals, African-Americans exhibited diminished excretion of not only kallikrein and potassium, but also aldosterone (P = 0.003), suggesting a mechanistic link between potassium and kallikrein excretion in their ethnic variations. CONCLUSIONS: Kallikrein excretion is influenced by several independent determinants, both hereditary (gender, ethnicity, and genetic risk of hypertension) and environmental (potassium intake and excretion). Ethnicity and environment may interact uniquely to influence kallikrein, as demonstrated by the case of African-Americans with diminutions of both kallikrein and potassium excretion. These results suggest a mechanism whereby kallikrein excretion is diminished in African-Americans, as well as therapeutic strategies to correct this deficiency. Finally, the identified determinants of kallikrein excretion will require analytic adjustment during genetic studies of this 'intermediate phenotype' in hypertension. Journal of Human Hypertension (2000) 14, 461-468

Gender differences in pain.

A review of the literature on gender and clinical pain reveals a disproportionate representation of women receiving treatment for many pain conditions and suggests that women report more severe pain, more frequent pain, and pain of longer duration than do men. Gender differences in pain perception have also been extensively studied in the laboratory, and ratings of experimentally induced pain also show some sex disparity, with females generally reporting lower pain thresholds and tolerance than males. However, there is little consensus on whether these apparent differences reflect the way men and women respond to pain, differing social rules for the expression of pain, or biologic differences in the way noxious stimuli are processed. In this paper, our working hypothesis is that the higher prevalence of chronic orofacial pain in women is a result of sex differences in generic pain mechanisms and of as-yet unidentified factors unique to the craniofacial system. We will review the evidence concerning gender differences in the prevalence of pain conditions, with a focus on orofacial pain conditions. Evidence and hypotheses concerning biologic and psychosocial factors that could influence prevalence rates will also be discussed.