Anticancer actions of carnosine in cellular models of prostate cancer.

Treatments for organ-confined prostate cancer include external beam radiation therapy, radical prostatectomy, radiotherapy/brachytherapy, cryoablation and high-intensity focused ultrasound. None of these are cancer-specific and are commonly accompanied by side effects, including urinary incontinence and erectile dysfunction. Moreover, subsequent surgical treatments following biochemical recurrence after these interventions are either limited or affected by the scarring present in the surrounding tissue. Carnosine (ß-alanyl-L-histidine) is a histidine-containing naturally occurring dipeptide which has been shown to have an anti-tumorigenic role without any detrimental effect on healthy cells; however, its effect on prostate cancer cells has never been investigated. In this study, we investigated the effect of carnosine on cell proliferation and metabolism in both a primary cultured androgen-resistant human prostate cancer cell line, PC346Flu1 and murine TRAMP-C1 cells. Our results show that carnosine has a significant dose-dependent inhibitory effect in vitro on the proliferation of both human (PC346Flu1) and murine (TRAMP-C1) prostate cancer cells, which was confirmed in 3D-models of the same cells. Carnosine was also shown to decrease adenosine triphosphate content and reactive species which might have been caused in part by the increase in SIRT3 also shown after carnosine treatment. These encouraging results support the need for further human in vivo work to determine the potential use of carnosine, either alone or, most likely, as an adjunct therapy to surgical or other conventional treatments.

Challenges in moving toward universal health coverage: rising cost of outpatient care among Vietnam's insured rural residents, 2006-2018.

OBJECTIVES: The aim of this study was to assess temporal trends in out-of-pocket (OOP) expenditures per outpatient contact by the insured residents in rural Vietnam. STUDY DESIGN: This was a repeated cross-sectional study. METHODS: Seven biennial waves from the Vietnam's Household Living Standard Survey covering the period 2006-2018 and a two-part model were used to assess temporal trends in OOP expenditures and its variations across various health facilities while controlling for a wide array of individual- and household-specific characteristics. RESULTS: The pattern of health facility utilization shifted steadily from commune health centers toward higher level government hospitals and private health facilities between 2006 and 2018. The regression results indicated an upward trend in the amount of OOP expenditures, with the amount of OOP expenditures incurred per outpatient contact being 40.3% higher in 2010-2012 than in 2006-2008 and by as much as 155.5% higher in 2018. These high-cost pressures were attenuated by 63%-65% when accounting for the types of health facility contacted. The cost inflation was more pronounced for care sought at higher level government hospitals and private hospitals than at other health facilities. CONCLUSION: The cost of accessing outpatient care rose sharply between 2006 and 2018, particularly for visits involving higher level government hospitals and private hospitals. These findings suggest that beside expanding the coverage over the transition path to universal coverage, efforts should be directed at reforming Vietnam's hospital-centric and fragmented delivery system as a way of containing costs and ensuring financial sustainability of social health insurance system.

Surgically Implanted Electrodes Enable Real-Time Finger and Grasp Pattern Recognition for Prosthetic Hands.

Currently available prosthetic hands are capable of actuating anywhere from five to 30 degrees of freedom (DOF). However, grasp control of these devices remains unintuitive and cumbersome. To address this issue, we propose directly extracting finger commands from the neuromuscular system via electrodes implanted in residual innervated muscles and regenerative peripheral nerve interfaces (RPNIs). Two persons with transradial amputations had RPNIs created by suturing autologous free muscle grafts to their transected median, ulnar, and dorsal radial sensory nerves. Bipolar electrodes were surgically implanted into their ulnar and median RPNIs and into their residual innervated muscles. The implanted electrodes recorded local electromyography (EMG) with Signal-to-Noise Ratios ranging from 23 to 350 measured across various movements. In a series of single-day experiments, participants used a high speed pattern recognition system to control a virtual prosthetic hand in real-time. Both participants were able to transition between 10 pseudo-randomly cued individual finger and wrist postures in the virtual environment with an average online accuracy of 86.5% and latency of 255 ms. When the set was reduced to five grasp postures, average metrics improved to 97.9% online accuracy and 135 ms latency. Virtual task performance remained stable across untrained static arm positions while supporting the weight of the prosthesis. Participants also used the high speed classifier to switch between robotic prosthetic grips and complete a functional performance assessment. These results demonstrate that pattern recognition systems can use the high-quality EMG afforded by intramuscular electrodes and RPNIs to provide users with fast and accurate grasp control. SUMMARY: Surgically implanted electrodes recorded finger-specific electromyography enabling reliable finger and grasp control of an upper limb prosthesis.

Severe injuries and household catastrophic health expenditure in Vietnam: findings from the Household Living Standard Survey 2014.

OBJECTIVES: To assess the extent that the presence of severe injuries among rural and urban household members is associated with household catastrophic expenditure. STUDY DESIGN: Vietnam's Household Living Standard Survey of 2014 was used for this study. METHODS: A two-level (household and community) logistic regression analysis was used to identify factors associated with catastrophic health expenditure. RESULTS: The incidence of catastrophic health expenditure was significantly higher in rural areas (3.1-11.7%) than in urban areas (1.4-6.1%). Households with members with severe injuries were significantly more likely to incur catastrophic health expenditure than those without severe injuries, and the increase was more pronounced for the rural poor and near poor (5.5-8.7 times) than for the rural rich (1.5-2.5 times). Having at least one inpatient contact at a higher level public hospital increased the risk of catastrophic health expenditure significantly for both rural and urban residents, and the increase was significantly greater among the rural residents than the urban residents. Having more household members with health insurance had little effect on the incidence of catastrophic health expenditure faced by urban residents, while it increased the incidence of catastrophic health expenditure faced by rural residents. CONCLUSION: The presence of severe injuries among household members was strongly associated with catastrophic health expenditure. To protect households against the financial consequences of severe injuries, efforts should be directed at injury prevention and strengthening the quality of primary and trauma care at the lower level public health facilities as well as extending the breadth and depths of insurance coverage.

Effects of market type and time of purchase on oxidative status and descriptive off-odors and off-flavors of beef in Vietnam.

The objective of the current study was to determine the effects of market type (super market - SM, indoor market - IM, open market - OM) and sampling time (at the opening - T0 and 4 h after the opening - T4) on antioxidant capacity, lipid oxidation, and descriptive sensory attributes of beef in Vietnam. Values of FC and TEAC were greater in OM beef than IM and SM (P < 0.001) and FC value was also greater at T4 than T0 (P = 0.038). The beef from SM had 7% greater TBARS than IM and OM (P = 0.003). Livery odor was less intense in raw beef from OM when compared to SM and IM (P ≤ 0.047). Sour odor in raw beef, and livery flavor in cooked beef was increased from T0 to T4 (P ≤ 0.035). Principal component analysis of descriptive sensory attributes indicated that FC and TEAC could predict partial livery flavor in cooked beef, but not off-odors in raw beef.

Influence of recent climatic events on the surface water storage of the Tonle Sap Lake.

Lakes and reservoirs have been identified as sentinels of climate change. Tonle Sap is the largest lake in both the Mekong Basin and Southeast Asia and because of the importance of its ecosystem, it is has been described as the "heart of the lower Mekong". Its seasonal cycle depends on the annual flood pulse governed by the flow of the Mekong River. This study provides an impact analysis of recent climatic events from El Niño 1997/1998 to El Niño 2015/2016 on surface storage variations in the Tonle Sap watershed determined by combining remotely sensed observations, multispectral images and radar altimetry from 1993 to 2017. The Lake's surface water volume variations are highly correlated with rainy season rainfall in the whole Mekong River Basin (R = 0.84) at interannual time-scale. Extreme droughts and floods can be observed when precipitation deficit and excess is recorded in both the Tonle Sap watershed and the Mekong River Basin during moderate to very strong El Niño/La Niña events (R = -0.70) enhanced by the Pacific Decadal Oscillation (R = -0.68). Indian and Western North Pacific Monsoons were identified as having almost equal influence. Below normal vegetation activity was observed during the first semester of 2016 due to the extreme drought in 2015.

Characteristics of persons who inject drugs and who witness opioid overdoses in Vietnam: a cross-sectional analysis to inform future overdose prevention programs.

BACKGROUND: Persons who use opioids have a high risk of overdose and associated mortality. In Vietnam, little is known about the characteristics of this population and the persons who are witness to those overdoses. One approach to combatting fatal overdose has been the use of peer interventions in which a friend or injecting partner administers overdose reversal medication, but availability in Vietnam of these medications is limited to pilot programs with aims to expand in the future (Le Minh and V.F. Go, Personal Communication, 2016). The primary objective of this paper is to explore the characteristics associated with witnessing three or more overdoses in a lifetime. METHODS: This cross-sectional analysis used baseline data from a four-arm randomized control trial conducted in Thai Nguyen, Vietnam, known as the Prevention for Positives project. One thousand six hundred seventy-three PWID were included in the analysis. We conducted bivariable and multivariable logistic regression to identify characteristics associated with witnessing three or more overdoses in a lifetime. Characteristics explored included education, employment, marital status, risky drug use behaviors, locations for accessing syringes, recent overdose, history of incarceration, drug treatment, and having slept outside in the past 3 months. RESULTS: Seventy-two percent (n = 1203) of participants had witnessed at least one overdose in their lifetime, and 46% had witnessed three or more overdoses (n = 765). In the multivariable model, having less than secondary education (AOR 0.70; 95% CI 0.57, 0.86), having slept outside in the past 3 months (AOR 1.77; 95% CI 1.31, 2.40), having a history of incarceration (AOR 1.33; 95% CI 1.07, 1.65), having a history of drug treatment (AOR 1.41; 95% CI 1.12, 1.77), experiencing a recent non-fatal overdose (AOR 3.84; 95% CI 2.36, 6.25), injecting drugs daily (AOR 1.79; 95% CI 1.45, 2.20), receptive needle sharing (AOR 1.30; 95% CI 1.04, 1.63), and number of years injecting (AOR 1.04; 95% CI 1.02, 1.07) were significantly associated with witnessing three or more overdoses. CONCLUSIONS: Targeted interventions are needed to train persons witnessing an overdose to administer overdose-reversal medication. This includes targeting persons prior to release from prisons, drug treatment centers, and those accessing syringe exchange programs. Additional research should assess the burden of witnessing an overdose as well as locations for medication distribution. Assessments of the training capacity and needs for implementing these programs among drug using peers in Vietnam are of the utmost importance.

Neural control of finger movement via intracortical brain-machine interface.

OBJECTIVE: Intracortical brain-machine interfaces (BMIs) are a promising source of prosthesis control signals for individuals with severe motor disabilities. Previous BMI studies have primarily focused on predicting and controlling whole-arm movements; precise control of hand kinematics, however, has not been fully demonstrated. Here, we investigate the continuous decoding of precise finger movements in rhesus macaques. APPROACH: In order to elicit precise and repeatable finger movements, we have developed a novel behavioral task paradigm which requires the subject to acquire virtual fingertip position targets. In the physical control condition, four rhesus macaques performed this task by moving all four fingers together in order to acquire a single target. This movement was equivalent to controlling the aperture of a power grasp. During this task performance, we recorded neural spikes from intracortical electrode arrays in primary motor cortex. MAIN RESULTS: Using a standard Kalman filter, we could reconstruct continuous finger movement offline with an average correlation of ρ = 0.78 between actual and predicted position across four rhesus macaques. For two of the monkeys, this movement prediction was performed in real-time to enable direct brain control of the virtual hand. Compared to physical control, neural control performance was slightly degraded; however, the monkeys were still able to successfully perform the task with an average target acquisition rate of 83.1%. The monkeys' ability to arbitrarily specify fingertip position was also quantified using an information throughput metric. During brain control task performance, the monkeys achieved an average 1.01 bits s-1 throughput, similar to that achieved in previous studies which decoded upper-arm movements to control computer cursors using a standard Kalman filter. SIGNIFICANCE: This is, to our knowledge, the first demonstration of brain control of finger-level fine motor skills. We believe that these results represent an important step towards full and dexterous control of neural prosthetic devices.

Long-Term Engraftment and Fetal Globin Induction upon BCL11A Gene Editing in Bone-Marrow-Derived CD34+ Hematopoietic Stem and Progenitor Cells.

To develop an effective and sustainable cell therapy for sickle cell disease (SCD), we investigated the feasibility of targeted disruption of the BCL11A gene, either within exon 2 or at the GATAA motif in the intronic erythroid-specific enhancer, using zinc finger nucleases in human bone marrow (BM) CD34+ hematopoietic stem and progenitor cells (HSPCs). Both targeting strategies upregulated fetal globin expression in erythroid cells to levels predicted to inhibit hemoglobin S polymerization. However, complete inactivation of BCL11A resulting from bi-allelic frameshift mutations in BCL11A exon 2 adversely affected erythroid enucleation. In contrast, bi-allelic disruption of the GATAA motif in the erythroid enhancer of BCL11A did not negatively impact enucleation. Furthermore, BCL11A exon 2-edited BM-CD34+ cells demonstrated a significantly reduced engraftment potential in immunodeficient mice. Such an adverse effect on HSPC function was not observed upon BCL11A erythroid-enhancer GATAA motif editing, because enhancer-edited CD34+ cells achieved robust long-term engraftment and gave rise to erythroid cells with elevated levels of fetal globin expression when chimeric BM was cultured ex vivo. Altogether, our results support further clinical development of the BCL11A erythroid-specific enhancer editing in BM-CD34+ HSPCs as an autologous stem cell therapy in SCD patients.

Natural orifice transluminal endoscopic surgery for colorectal cancer.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has theoretical advantages over other approaches. METHODS: This was a prospective cohort study of colorectal cancers operated on by NOTES (transanally for rectal tumours, transvaginally for sigmoid tumours) between December 2013 and December 2015, with a minimum follow-up of 1 year. Eligibility criteria included ASA fitness grade I-III, BMI below 25 kg/m2 and TNM stage T3 N0 M0. Exclusion criteria included pregnancy or distant metastasis. The anastomosis was either handsewn or performed mechanically. RESULTS: Sixteen patients were operated on by a transanal and four by a transvaginal approach. There were ten men and ten women, with a mean(s.d.) age of 55·6(12·1) years. Mean BMI was 22·4(2·6) kg/m2. Four anterior, 11 low anterior and five intersphincteric resections were performed for 16 rectal and four low sigmoid tumours. The mean duration of surgery was 258(11) min. No conversion to laparotomy was needed, and there were no deaths. Five patients required additional ports, for intraoperative bleeding (1), suture of an intraoperative urethral injury with covering ileostomy (1) and difficulty in dissection (3). One patient had an anastomotic leak requiring transanal closure and ileostomy on day 7. Both ileostomies were closed after 2 months. The mean hospital stay was 6·4(1·8) days. All resections were R0. CONCLUSION: In carefully selected patients NOTES for colorectal cancer resection was feasible and effective.

Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque.

OBJECTIVE: Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. APPROACH: The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. MAIN RESULTS: No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey's finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. SIGNIFICANCE: The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

Collection of Oral Fluids Using Cotton Ropes as a Sampling Method to Detect Foot-and-Mouth Disease Virus Infection in Pigs.

In high-density farming practices, it is important to constantly monitor for infectious diseases, especially diseases that have the potential to spread rapidly between holdings. Pigs are known to amplify foot-and-mouth disease (FMD) by excreting large amounts of virus, and it is therefore important to detect the virus quickly and accurately to minimize the spread of disease. Ropes were used to collect oral fluid samples from pigs, and each sample was compared to saliva samples collected from individual animals by detecting FMD virus RNA using real-time PCR. Two different experiments are described where groups of pigs were infected with different serotypes of FMD virus, either with or without vaccination, and unvaccinated pigs were kept in aerosol contact. The sensitivity of the rope sampling varied between 0.67 and 0.92, and the statistical agreement between this method and individual sampling ranged from substantial to moderate for the two different serotypes. The ease of collecting oral fluids using ropes together with the high sensitivity of subsequent FMD detection through PCR indicates that this could be a useful method to monitor pig populations for FMD virus infection. With further validation of the sensitivity of detection of FMD virus RNA, this can be a cost-effective, non-invasive diagnostic tool.

CT Colonography Reporting and Data System (C-RADS): benchmark values from a clinical screening program.

OBJECTIVE: The CT Colonography Reporting and Data System (C-RADS) is a well-recognized standard for reporting findings at CT colonography (CTC). However, few data on benchmark values for clinical performance have been published to date, especially for screening. The purpose of this study was to establish baseline C-RADS values for CTC screening. SUBJECTS AND METHODS: From 2005 to 2011, 6769 asymptomatic adults (3110 men and 3659 women) 50-79 years old (mean [± SD] age, 56.7 ± 6.1 years) were enrolled for first-time CTC screening at a single center. CTC results were prospectively classified according to C-RADS for both colorectal and extracolonic findings. C-RADS classification rates and outcomes for positive patients were analyzed. RESULTS: C-RADS classification rates for colorectal evaluation were C0 (0.7%), C1 (85.0%), C2 (8.6%), C3 (5.2%), and C4 (0.6%). Overall, 14.3% of subjects were positive (C2-C4), and positive findings were more frequent among men (17.5%) than women (11.6%; p < 0.0001). Positivity also increased with age, from 13.4% of patients 50-64 years old to 21.8% of patients 65-79 years old (p < 0.0001). Regarding extracolonic evaluation, 86.6% of patients were either negative for extracolonic findings or had unimportant extracolonic findings (E1 or E2). Likely unimportant but indeterminate extracolonic findings where further workup might be indicated (E3) were found in 11.3% of patients, whereas 2.1% had likely important extracolonic findings (E4). Overall, E3 and E4 rates were increased for older (p < 0.0001) and female (p = 0.008) cohorts. CONCLUSION: C-RADS results from our initial experience with CTC screening may serve as an initial benchmark for program comparison and quality assurance measures.

Carpet lesions detected at CT colonography: clinical, imaging, and pathologic features.

PURPOSE: To describe carpet lesions (laterally spreading tumors ≥ 3 cm) detected at computed tomographic (CT) colonography, including their clinical, imaging, and pathologic features. MATERIALS AND METHODS: The imaging reports for 9152 consecutive adults undergoing initial CT colonography at a tertiary center were reviewed in this HIPAA-compliant, institutional review board-approved retrospective study to identify all potential carpet lesions detected at CT colonography. Carpet lesions were defined as morphologically flat, laterally spreading tumors 3 cm or larger. For those patients with neoplastic carpet lesions, CT colonography studies were analyzed to determine maximal lesion width and height, oral contrast material coating, segmental location, and computer-aided detection (CAD) findings. Demographic data and details of clinical treatment in these patients were reviewed. RESULTS: Eighteen carpet lesions in 18 patients (0.2%; mean age, 67.1 years; eight men, 10 women) were identified and were subsequently confirmed at colonoscopy and pathologic examination among 20 potential flat masses (≥3 cm) prospectively identified at CT colonography (there were two nonneoplastic rectal false-positive findings). No additional neoplastic carpet lesions were found in the cohort undergoing colonoscopy after CT colonography and/or surgery (there were no false-negatives). Mean lesion width was 46.5 mm (range, 30-80 mm); mean lesion height was 7.9 mm (range, 4-14 mm). Surface retention of oral contrast material was noted in all 18 cases. All but two lesions were located in the distal rectosigmoid or proximal right colon. At CAD, 17 (94.4%) lesions were detected (mean, 6.2 CAD marks per lesion). Sixteen lesions (88.9%) demonstrated advanced histologic features, including a villous component (n = 11), high-grade dysplasia (n = 4), and invasive cancer (n = 5). Sixteen patients (88.9%) required surgical treatment for complete excision. CONCLUSION: CT colonography can effectively depict carpet lesions. Common features in this series included older patient age, rectal or cecal location, surface coating with oral contrast material, multiple CAD hits, advanced yet typically benign histologic features, and surgical treatment.

Relative performance of alkynes in copper-catalyzed azide-alkyne cycloaddition.

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) has found numerous applications in a variety of fields. We report here only modest differences in the reactivity of various classes of terminal alkynes under typical bioconjugative and preparative organic conditions. Propargyl compounds represent an excellent combination of azide reactivity, ease of installation, and cost. Electronically activated propiolamides are slightly more reactive, at the expense of increased propensity for Michael addition. Certain alkynes, including tertiary propargyl carbamates, are not suitable for bioconjugation due to copper-induced fragmentation. A fluorogenic probe based on such reactivity is available in one step from rhodamine 110 and can be useful for optimization of CuAAC conditions.

HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam.

BACKGROUND: Access to antiretroviral therapy (ART) for HIV-infected individuals in Vietnam is rapidly expanding, but there are limited data on HIV drug resistance (HIVDR) to guide ART strategies. METHODS: We retrospectively conducted HIVDR testing in 220 ART-naive individuals recruited to a randomized controlled trial of immediate versus deferred ART in individuals with HIV-associated tuberculous meningitis in Ho Chi Minh City (HCMC) from 2005-2008. HIVDR mutations were identified by population sequencing of the HIV pol gene and were defined based on 2009 WHO surveillance drug resistance mutations (SDRMs). RESULTS: We successfully sequenced 219/220 plasma samples of subjects prior to ART; 218 were subtype CRF01_AE and 1 was subtype B. SDRMs were identified in 14/219 (6.4%) subjects; 8/14 were resistant to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs; T69D, L74V, V75M, M184V/I and K219R), 5/14 to non-nucleoside reverse transcriptase inhibitors (NNRTIs; K103N, V106M, Y181C, Y188C and G190A), 1/14 to both NRTIs and NNRTIs (D67N and Y181C) and none to protease inhibitors. After 6 months of ART, eight subjects developed protocol-defined virological failure. HIVDR mutations were identified in 5/8 subjects. All five had mutations with high-level resistance to NNRTIs and three had mutations with high-level resistance to NRTIs. Due to a high early mortality rate (58%), the effect of pre-existing HIVDR mutations on treatment outcome could not be accurately assessed. CONCLUSIONS: The prevalence of WHO SDRMs in ART-naive individuals with HIV-associated tuberculous meningitis in HCMC from 2005-2008 is 6.4%. The SDRMs identified conferred resistance to NRTIs and/or NNRTIs, reflecting the standard first-line ART regimens in Vietnam.

Degradable conjugates from oxanorbornadiene reagents.

Oxanorbornadienedicarboxylate (OND) reagents were explored for purposes of binding and releasing drugs from serum albumins as representative macromolecular carriers. Being highly reactive Michael acceptors, ONDs form adducts with thiols and amines, which then undergo retro-Diels-Alder fragmentation. A study of more than 30 model adducts revealed a number of modifications that can be used to influence adduct stability. For the most reactive OND linkers, the labeling of the single available bovine serum albumin (BSA) cysteine residue was complete within minutes at a mid-micromolar concentration of reactants. While a selectivity of greater than 1000-fold for thiol over amine was observed with model amino acids, the labeling of protein amines with ONDs is fast enough to be practical, as demonstrated by the reaction with thiol-depleted BSA. The OND-amine adducts were found to be up to 15 times more stable than OND-thiol adducts, and to be sensitive to acid by virtue of a stereochemically dependent acceleration of cycloreversion. The release rate of fluorescent cargo from serum albumins was tuned by selecting the coupling partners: the available half-lives ranged from 40 min to 7 days at 37 °C. Such versatility of release profiles from protein carriers, controlled by the nature of the OND linkage, is a useful addition to the drug delivery toolbox.

Recent avian influenza virus A/H5N1 evolution in vaccinated and unvaccinated poultry from farms in Southern Vietnam, January-March 2010.

We report 15 new avian influenza virus A/H5N1 haemagglutinin (HA) sequences sampled from visibly sick domestic poultry in southern Vietnam, between 1 January 2010 and 6 March 2010. These HA sequences form a new sub-clade of the clade 1 H5N1 viruses that have been circulating in Vietnam since 2003/2004. The viruses are characterized by a change from isoleucine to valine at position 514 (I514V) and are 1.8% divergent at the nucleotide level from HA sequences sampled in Vietnam in 2007. Five new amino acid changes were observed at previously identified antigenic sites, and three were located within structural elements of the receptor-binding domain. One new mutation removed a potential N-linked glycosylation site, and a methionine insertion was observed in one virus at the polybasic cleavage site. Five of these viruses were sampled from farms where poultry were vaccinated against H5N1, but there was no association between observed amino acid changes and flock vaccination status. Despite the current lack of evidence for antigenic drift or immune escape in Vietnamese H5N1 viruses, continued surveillance remains a high priority.

Five-step clinical assessment in spastic paresis.

Among the three main factors of motor impairment that emerge in chronological order following a lesion to central motor pathways, the last two antagonize movement: 1) stretch-sensitive paresis, a reduction of agonist motor unit recruitment upon voluntary command, worsened by antagonist stretch; 2) soft tissue contracture, and 3) muscle overactivity. Types of muscle overactivity include 1) spasticity, an increase in the velocity-dependent response to muscle stretch, measured at rest; 2) spastic dystonia, i.e., chronic tonic muscle activity at rest, sensitive to stretch of the dystonic muscle and 3) spastic co-contraction, an inappropriate degree of antagonistic contraction during voluntary agonist command, sensitive to stretch of the co-contracting muscle. A five-step clinical assessment may closely parallel this phenomenology, in which the first four steps aim at quantifying the antagonistic potential of each muscle group. Step-1 measures passive range of motion, i.e., the angle of arrest upon slow stretch of the muscle group assessed (minimizing spastic dystonia), which provides insight on soft tissue length and extensibility. Step-2 measures the angle of catch or clonus upon fast passive stretch of the muscle group assessed, which provides insight on stretch reflex excitability. Step-3 measures the range of active motion against the muscle group assessed, a net result of agonist recruitment minus the combined resistance from passive soft tissue stiffness and spastic co-contraction in the muscle group assessed. Step-4 measures the maximal frequency of rapid alternating movements along the maximal active range of motion, evaluating Step-3 performance repeatability. Step-5 evaluates active function, using for example a walking test (10 m or 2 min) for lower limb and the Modified Frenchay Scale for upper limb assessment, and perceived function through patient global subjective assessment.