Strengthening cardiac therapy pipelines using human pluripotent stem cell-derived cardiomyocytes.

Advances in hiPSC isolation and reprogramming and hPSC-CM differentiation have prompted their therapeutic application and utilization for evaluating potential cardiovascular safety liabilities. In this perspective, we showcase key efforts toward the large-scale production of hiPSC-CMs, implementation of hiPSC-CMs in industry settings, and recent clinical applications of this technology. The key observations are a need for traceable gender and ethnically diverse hiPSC lines, approaches to reduce cost of scale-up, accessible clinical trial datasets, and transparent guidelines surrounding the safety and efficacy of hiPSC-based therapies.

Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes.

Perlecan (HSPG2), a heparan sulfate proteoglycan similar to agrin, is key for extracellular matrix (ECM) maturation and stabilization. Although crucial for cardiac development, its role remains elusive. We show that perlecan expression increases as cardiomyocytes mature in vivo and during human pluripotent stem cell differentiation to cardiomyocytes (hPSC-CMs). Perlecan-haploinsuffient hPSCs (HSPG2+/-) differentiate efficiently, but late-stage CMs have structural, contractile, metabolic, and ECM gene dysregulation. In keeping with this, late-stage HSPG2+/- hPSC-CMs have immature features, including reduced ⍺-actinin expression and increased glycolytic metabolism and proliferation. Moreover, perlecan-haploinsuffient engineered heart tissues have reduced tissue thickness and force generation. Conversely, hPSC-CMs grown on a perlecan-peptide substrate are enlarged and display increased nucleation, typical of hypertrophic growth. Together, perlecan appears to play the opposite role of agrin, promoting cellular maturation rather than hyperplasia and proliferation. Perlecan signaling is likely mediated via its binding to the dystroglycan complex. Targeting perlecan-dependent signaling may help reverse the phenotypic switch common to heart failure.

2-year survival estimation for decompensated cirrhosis patients of prognostic scoring systems.

OBJECTIVE: Prognostic models proposed for cirrhotic patients' survival have not been satisfactorily investigated in the Vietnam population, especially in the medium-term period. PATIENTS AND METHODS: In this prospective study, we enrolled a total of 904 patients admitted to Hepato-Gastroenterology Center, Bach Mai Hospital from December 2019 to November 2021 and calculated their CP, MELD, MELD-Na score, IMELD, Refit MELD, and Refit MELD-Na after 2-year follow-up to compare their survival prognosis. RESULTS: The mean age of the patients was 53.8 ±10.8 years, and males constituted 91%. Compared with the surviving group, deceased patients had statistically significant lower albumin, higher INR, serum bilirubin, and creatinine levels with higher means of all prognostic scores. RefitMELD score had the highest AUC (0.768), followed by MELD (0.766), and the lowest belonged to RefitMELDNa (0.669). CONCLUSIONS: In conclusion, deceased patients had significantly higher values of Child-Pugh score and all MELD-based scores than survival. RefitMELD is the most reliable scoring system to predict 2-year mortality in patients with decompensated liver cirrhosis.

Chronic activation of human cardiac fibroblasts in vitro attenuates the reversibility of the myofibroblast phenotype.

Activation of cardiac fibroblasts and differentiation to myofibroblasts underlies development of pathological cardiac fibrosis, leading to arrhythmias and heart failure. Myofibroblasts are characterised by increased α-smooth muscle actin (α-SMA) fibre expression, secretion of collagens and changes in proliferation. Transforming growth factor-beta (TGF-ß) and increased mechanical stress can initiate myofibroblast activation. Reversibility of the myofibroblast phenotype has been observed in murine cells but has not been explored in human cardiac fibroblasts. In this study, chronically activated adult primary human ventricular cardiac fibroblasts and human induced pluripotent stem cell derived cFbs (hiPSC-cFbs) were used to investigate the potential for reversal of the myofibroblast phenotype using either subculture on soft substrates or TGF-ß receptor inhibition. Culture on softer plates (25 or 2 kPa Young's modulus) did not alter proliferation or reduce expression of α-SMA and collagen 1. Similarly, culture of myofibroblasts in the presence of TGF-ß inhibitor did not reverse myofibroblasts back to a quiescent phenotype. Chronically activated hiPSC-cFbs also showed attenuated response to TGF-ß receptor inhibition and inability to reverse to quiescent fibroblast phenotype. Our data demonstrate substantial loss of TGF-ß signalling plasticity as well as a loss of feedback from the surrounding mechanical environment in chronically activated human myofibroblasts.

Stent-Assisted Coiling in the Treatment of Unruptured Intracranial Aneurysms: A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: Stent-assisted coiling may improve angiographic results of endovascular treatment of unruptured intracranial aneurysms compared with coiling alone, but this has never been shown in a randomized trial. MATERIALS AND METHODS: The Stenting in the Treatment of Aneurysm Trial was an investigator-led, parallel, randomized (1:1) trial conducted in 4 university hospitals. Patients with intracranial aneurysms at risk of recurrence, defined as large aneurysms (≥10 mm), postcoiling recurrent aneurysms, or small aneurysms with a wide neck (≥4 mm), were randomly allocated to stent-assisted coiling or coiling alone. The composite primary efficacy outcome was "treatment failure," defined as initial failure to treat the aneurysm; aneurysm rupture or retreatment during follow-up; death or dependency (mRS > 2); or an angiographic residual aneurysm adjudicated by an independent core laboratory at 12 months. The primary hypothesis (revised for slow accrual) was that stent-assisted coiling would decrease treatment failures from 33% to 15%, requiring 200 patients. Primary analyses were intent to treat. RESULTS: Of 205 patients recruited between 2011 and 2021, ninety-four were allocated to stent-assisted coiling and 111 to coiling alone. The primary outcome, ascertainable in 203 patients, was reached in 28/93 patients allocated to stent-assisted coiling (30.1%; 95% CI, 21.2%-40.6%) compared with 30/110 (27.3%; 95% CI, 19.4%-36.7%) allocated to coiling alone (relative risk = 1.10; 95% CI, 0.7-1.7; P = .66). Poor clinical outcomes (mRS >2) occurred in 8/94 patients allocated to stent-assisted coiling (8.5%; 95% CI, 4.0%-16.6%) compared with 6/111 (5.4%; 95% CI, 2.2%-11.9%) allocated to coiling alone (relative risk = 1.6; 95% CI, 0.6%-4.4%; P = .38). CONCLUSIONS: The STAT trial did not show stent-assisted coiling to be superior to coiling alone for wide-neck, large, or recurrent unruptured aneurysms.

Relationship of Recurrence Rate with some Characteristics in Patients with Thyroid Carcinoma.

Background: Determining the clinical and subclinical characteristics related to the recurrence status in patients with a thyroid carcinoma has great significance for prognosis, prediction of recurrence and monitoring of treatment outcomes. This study aimed to determine the association between recurrence rate and some characteristics in patients with thyroid carcinoma. Patients and Methods: The study was conducted by descriptive method with longitudinal follow-up on 102 thyroid carcinoma patients at 103 Military Hospital, Hanoi, Vietnam, from July 2013 to December 2016. Results: Univariate analysis showed that there was a relationship between the recurrence characteristics in the studied patients and the characteristics of lymph node metastasis (P = 0.026; OR = 15; 95% CI = 1.4-163.2) and BRAF V600E mutation status (P = 0.01; OR = 3.41; 95% CI = 1.31-8.88). When analysing the multivariable Logistic regression model, there was a positive correlation between the occurrence of BRAF V600E gene mutation (P = 0.032; OR = 17.649; 95% CI = 1.290-241.523) and male sex (P = 0.036; OR = 12.788; 95% CI = 1.185-137.961) and the occurrence of recurrence in study patients. The mean time to relapse was earlier in male patients than in female patients (P = 0.02). The mean time to relapse in patients with the BRAF V600E mutation (31.81 ± 1.14 months) was shorter than the mean time to relapse in the group without the mutation (57.82 ± 2.08 months) (P = 0.01). The group of patients with mutations in the BRAF V600E gene increased the risk of recurrence compared with the group without the mutation (HR = 9.14, P = 0.04). Conclusion: There is a positive correlation between recurrence and masculinity, lymph node metastasis and the occurrence of BRAF V600E mutations in thyroid carcinoma patients.

Mortality Burden due to Exposure to Outdoor Fine Particulate Matter in Hanoi, Vietnam: Health Impact Assessment.

Objective: This study reports the mortality burden due to PM2.5 exposure among adults (age >25) living in Hanoi in 2017. Methods: We applied a health impact assessment methodology with the global exposure mortality model and a PM2.5 map with 3 × 3 km resolution derived from multiple data sources. Results: The annual average PM2.5 concentration for each grid ranged from 22.1 to 37.2 µg/m³. The district average concentration values ranged from 26.9 to 37.2 µg/m³, which means that none of the 30 districts had annual average values below the Vietnam Ambient National Standard of 25 µg/m3. Using the Vietnam Ambient National Standard as the reference standard, we estimated that 2,696 deaths (95% CI: 2,225 to 3,158) per year were attributable to exposure to elevated PM2.5 concentrations in Hanoi. Using the Interim Target 4 value of 10 µg/m3 as the reference standard, the number of excess deaths attributable to elevated PM2.5 exposure was 4,760 (95% CI: 3,958-5,534). Conclusion: A significant proportion of deaths in Hanoi could be avoided by reducing air pollution concentrations to a level consistent with the Vietnam Ambient National Standard.

Antimicrobial resistance tendency and collateral sensitivity of Staphylococcus aureus adapted to antibiotics or extracts of medicinal plants grown in Viet Nam.

Antimicrobial resistance has silently turned into one of the biggest threats to global health, marking the fall of the Golden age of antibiotics. In the search for antibiotic replacement or enhancement, plant-derived natural compounds have attracted lots of interest. Even though firmly believed, the low-resistance tendency of pathogenic bacteria against plant extracts has been scarcely demonstrated. In this study, we investigated the antibacterial activities of diethyl ether extracts from six medicinal plants grown in Viet Nam against Staphylococcus aureus and its variants, which were in vitro adapted to the same extracts. After 30 passages of S. aureus growing under sub-lethal concentrations of plant extracts or antibiotics, the bacteria slowly adapted to the extracts while rapidly resisting the antibiotics. Most of the resulting strains obtained from the adaptation to plant extracts were collaterally sensitive to antibiotics. In contrast, antibiotic-adapted strains showed cross-resistance to both antibiotics and extracts. The findings provided evidence of the low-resistance tendency of S. aureus to antimicrobial plant extracts. It is the first time a collateral antibiotic sensitivity of S. aureus adapted to natural compounds has been observed, suggesting an alternative approach to fight antibiotic resistance.

Differentiation and Characterization of Human Pluripotent Stem Cell-Derived Cardiac Endothelial Cells for In Vitro Applications.

Various protocols have been developed to generate endothelial cells for disease modeling, angiogenesis, vascular regeneration, and drug screening. These protocols often require cell sorting, as most differentiation strategies result in a heterogenous population of endothelial cells (ECs). For any given model system, one important consideration is choosing the appropriate EC subtype, as different EC populations have unique molecular signatures.Herein, we describe a protocol for cardiac EC differentiation and a protocol for endothelial cell characterization. This protocol is aimed at investigating differentiation efficiency by measuring endothelial lineage markers, CD31, VE-Cadherin, and VEGFR2 by flow cytometry. Collectively, these protocols comprise the tools required to generate cardiac ECs efficiently and reproducibly from different hPSC lines without the need for cell sorting. Our protocol adds to the panel of hPSCs for cardiac EC differentiation and addresses reproducibility concerns of hPSC-based experiments. The approaches described are also applicable for complex model generation where multiple cardiovascular cell types are involved and may assist in optimizing differentiations for different cell lineages, including cardiomyocytes, cardiac endothelial cells, and cardiac fibroblasts.

Noninvasive Angiographic Results of Clipped or Coiled Intracranial Aneurysms: An Inter- and Intraobserver Reliability Study.

BACKGROUND AND PURPOSE: Noninvasive angiography is commonly used to assess the outcome of surgical or endovascular treatment of intracranial aneurysms in clinical series or randomized trials. We sought to assess whether a standardized 3-grade classification system could be reliably used to compare the CTA and MRA results of both treatments. MATERIALS AND METHODS: An electronic portfolio composed of CTAs of 30 clipped and MRAs of 30 coiled aneurysms was independently evaluated by 24 raters of diverse experience and training backgrounds. Twenty raters performed a second evaluation 1 month later. Raters were asked which angiographic grade and management decision (retreatment; close or long-term follow-up) would be most appropriate for each case. Agreement was analyzed using the Krippendorff α (αK) statistic, and the relationship between angiographic grade and clinical management choice, using the Fisher exact and Cramer V tests. RESULTS: Interrater agreement was substantial (αK = 0.63; 95% CI, 0.55-0.70); results were slightly better for MRA results of coiling (αK = 0.69; 95% CI, 0.56-0.76) than for CTA results of clipping (αK = 0.58; 95% CI, 0.44-0.69). Intrarater agreement was substantial to almost perfect. Interrater agreement regarding clinical management was moderate for both clipped (αK = 0.49; 95% CI, 0.32-0.61) and coiled subgroups (αK = 0.47; 95% CI, 0.34-0.54). The choice of clinical management was strongly associated with the size of the residuum (mean Cramer V = 0.77 [SD, 0.14]), but complete occlusions (grade 1) were followed more closely after coiling than after clipping (P = .01). CONCLUSIONS: A standardized 3-grade scale was found to be a reliable and clinically meaningful tool to compare the results of clipping and coiling of aneurysms using CTA or MRA.

Dietary soluble non-starch polysaccharide level and composition influences grower and finisher phase performance, excreta moisture content and total tract nutrient digestibility in broilers.

1. The aim of this study was to examine the impact of dietary soluble non-starch polysaccharide (sNSP) level and composition on grower and finisher phase performance, total tract nutrient digestibility and excreta moisture content in broiler chickens.2. Cobb 500 broilers (n = 1080) were fed 12 dietary treatments; four diets with differing primary grain sources (barley, corn, sorghum and wheat) and three different sNSP levels (low, medium and high). Diets were formulated to have similar protein and energy levels but differing sNSP levels, induced by manipulating the quantity of the ingredients in the diet. The diets were fed in three phases, starter (d 0-12), grower (d 12-23) and finisher (d 23-31).3. For birds aged d 23 and 31, total pen body weight and feed intake were determined, and fresh excreta and litter samples were collected per pen. Dry matter (DM) content was measured in the excreta and litter samples. Total tract DM digestibility, apparent metabolisable energy corrected to nitrogen (AMEn), and soluble and insoluble NSP and free oligosaccharide degradability were evaluated.4. In birds fed the sorghum- and corn-based diets, feeding high sNSP resulted in a lower cFCR at d 0-23 compared to low sNSP (P = 0.004 and P = 0.044, respectively). In birds fed the corn-based diet, feeding low sNSP resulted in the lowest litter DM but highest DM digestibility at d 23 (P = 0.045 and P < 0.001) and d 31 (P = 0.022 and P = 0.008). For all diets, degradability of sNSP was higher and insoluble NSP was lower when feeding low compared to high sNSP (P < 0.001). In birds fed the barley- and sorghum-based diets, AMEn was lower when feeding the low compared to high sNSP level (P < 0.001 and P = 0.016, respectively).6. Results from this study showed that level of dietary sNSP impacts broiler productive performance and nutrient utilisation.

The use of fluorescence correlation spectroscopy to monitor cell surface ß2-adrenoceptors at low expression levels in human embryonic stem cell-derived cardiomyocytes and fibroblasts.

The importance of cell phenotype in determining the molecular mechanisms underlying ß2 -adrenoceptor (ß2AR) function has been noted previously when comparing responses in primary cells and recombinant model cell lines. Here, we have generated haplotype-specific SNAP-tagged ß2AR human embryonic stem (ES) cell lines and applied fluorescence correlation spectroscopy (FCS) to study cell surface receptors in progenitor cells and in differentiated fibroblasts and cardiomyocytes. FCS was able to quantify SNAP-tagged ß2AR number and diffusion in both ES-derived cardiomyocytes and CRISPR/Cas9 genome-edited HEK293T cells, where the expression level was too low to detect using standard confocal microscopy. These studies demonstrate the power of FCS in investigating cell surface ß2ARs at the very low expression levels often seen in endogenously expressing cells. Furthermore, the use of ES cell technology in combination with FCS allowed us to demonstrate that cell surface ß2ARs internalize in response to formoterol-stimulation in ES progenitor cells but not following their differentiation into ES-derived fibroblasts. This indicates that the process of agonist-induced receptor internalization is strongly influenced by cell phenotype and this may have important implications for drug treatment with long-acting ß2AR agonists.

Reliability of the Diagnosis of Cerebral Vasospasm Using Catheter Cerebral Angiography: A Systematic Review and Inter- and Intraobserver Study.

BACKGROUND AND PURPOSE: Conventional angiography is the benchmark examination to diagnose cerebral vasospasm, but there is limited evidence regarding its reliability. Our goals were the following: 1) to systematically review the literature on the reliability of the diagnosis of cerebral vasospasm using conventional angiography, and 2) to perform an agreement study among clinicians who perform endovascular treatment. MATERIALS AND METHODS: Articles reporting a classification system on the degree of cerebral vasospasm on conventional angiography were systematically searched, and agreement studies were identified. We assembled a portfolio of 221 cases of patients with subarachnoid hemorrhage and asked 17 raters with different backgrounds (radiology, neurosurgery, or neurology) and experience (junior ≤10 and senior >10 years) to independently evaluate cerebral vasospasm in 7 vessel segments using a 3-point scale and to evaluate, for each case, whether findings would justify endovascular treatment. Nine raters took part in the intraobserver reliability study. RESULTS: The systematic review showed a very heterogeneous literature, with 140 studies using 60 different nomenclatures and 21 different thresholds to define cerebral vasospasm, and 5 interobserver studies reporting a wide range of reliability (κ = 0.14-0.87). In our study, only senior raters reached substantial agreement (κ ≥ 0.6) on vasospasm of the supraclinoid ICA, M1, and basilar segments and only when assessments were dichotomized (presence or absence of ≥50% narrowing). Agreement on whether to proceed with endovascular management of vasospasm was only fair (κ ≤ 0.4). CONCLUSIONS: Research on cerebral vasospasm would benefit from standardization of definitions and thresholds. Dichotomized decisions by experienced readers are required for the reliable angiographic diagnosis of cerebral vasospasm.

Optical properties and stability of small hollow gold nanoparticles.

In the current work, small hollow Au nanoparticles (d ≈ 16 nm) with excellent thermal stability and high photo-thermal conversion efficiency, which have great potential for use in photo-thermal cancer therapy, were prepared through galvanic replacement reaction between Ag nano-templates and gold salt. The position of surface plasmon resonance (SPR) bands for these nanoparticles could be tuned by varying the amount of gold salt. The hydrophobic hollow nanostructures were made water-dispersible by being encapsulated with poly(maleic anhydride-alt-1-octadecene) - PMAO. The obtained nanostructures were stable in an aqueous solution of NaCl with concentration up to 280 mM. The hollow gold nanoparticles (HGNPs) were then heated using an 808 nm laser at different power densities, the obtained data showed that they are highly photo-thermal stable under a high power density laser up to 1.6 W cm-2 after three circles of irradiation at 20 min per circle (20 min continuous irradiation for each circle). The facile synthesis of small size HGNPs with a plasmon peak in the near infrared range, colloidal and photo-thermal stability, and high capacity of conversion of photon energy into heat makes them a promising material for photo-thermal and imaging applications.

CRISPR/Cas9-mediated generation and analysis of N terminus polymorphic models of ß2AR in isogenic hPSC-derived cardiomyocytes.

During normal- and patho-physiological situations, the behavior of the beta2-adrenoreceptor (ß2AR) is influenced by polymorphic variants. The functional impact of such polymorphisms has been suggested from data derived from genetic association studies, in vitro experiments with primary cells, and transgenic overexpression models. However, heterogeneous genetic background and non-physiological transgene expression levels confound interpretation, leading to conflicting mechanistic conclusions. To overcome these limitations, we used CRISPR/Cas9 gene editing technology in human pluripotent stem cells (hPSCs) to create a unique suite of four isogenic homozygous variants at amino acid positions 16(G/R) and 27(G/Q), which reside in the N terminus of the ß2AR. By producing cardiomyocytes from these hPSC lines, we determined that at a functional level ß2AR signaling dominated over ß1AR . Examining changes in beat rates and responses to isoprenaline, Gi coupling, cyclic AMP (cAMP) production, downregulation, and desensitization indicated that responses were often heightened for the GE variant, implying differential dominance of both polymorphic location and amino acid substitution. This finding was corroborated, since GE showed hypersensitivity to doxorubicin-induced cardiotoxicity relative to GQ and RQ variants. Thus, understanding the effect of ß2AR polymorphisms on cardiac response to anticancer therapy may provide a route for personalized medicine and facilitate immediate clinical impact.

Does Increasing Packing Density Using Larger Caliber Coils Improve Angiographic Results of Embolization of Intracranial Aneurysms at 1 Year: A Randomized Trial.

BACKGROUND AND PURPOSE: The impact of increased aneurysm packing density on angiographic outcomes has not been studied in a randomized trial. We sought to determine the potential for larger caliber coils to achieve higher packing densities and to improve the angiographic results of embolization of intracranial aneurysms at 1 year. MATERIALS AND METHODS: Does Embolization with Larger Coils Lead to Better Treatment of Aneurysms (DELTA) was an investigator-initiated multicenter prospective, parallel, randomized, controlled clinical trial. Patients had 4- to 12-mm unruptured aneurysms. Treatment allocation to either 15- (experimental) or 10-caliber coils (control group) was randomized 1:1 using a Web-based platform. The primary efficacy outcome was a major recurrence or a residual aneurysm at follow-up angiography at 12 ± 2 months adjudicated by an independent core lab blinded to the treatment allocation. Secondary outcomes included indices of treatment success and standard safety outcomes. Recruitment of 564 patients was judged necessary to show a decrease in poor outcomes from 33% to 20% with 15-caliber coils. RESULTS: Funding was interrupted and the trial was stopped after 210 patients were recruited between November 2013 and June 2017. On an intent-to-treat analysis, the primary outcome was reached in 37 patients allocated to 15-caliber coils and 36 patients allocated to 10-caliber coils (OR = 0.931; 95% CI, 0.528-1.644; P = .885). Safety and other clinical outcomes were similar. The 15-caliber coil group had a higher mean packing density (37.0% versus 26.9%, P = .0001). Packing density had no effect on the primary outcome when adjusted for initial angiographic results (OR = 1.001; 95% CI, 0.981-1.022; P = .879). CONCLUSIONS: Coiling of aneurysms randomized to 15-caliber coils achieved higher packing densities compared with 10-caliber coils, but this had no impact on the angiographic outcomes at 1 year, which were primarily driven by aneurysm size and initial angiographic results.

Progress towards rabies control and elimination in Vietnam.

Rabies is a fatal viral disease that causes an estimated 59,000 human deaths each year. The majority of these deaths occur in developing countries in Asia. Canine rabies is endemic to Vietnam, which is, however, moving towards the disease's elimination. Many countries, such as Vietnam, have invested tremendous resources in controlling rabies, highlighting the goal of regional and global elimination of this neglected disease. In Vietnam, rabies is recognised as one of five high-priority, zoonotic diseases by the Ministry of Health and the Ministry of Agriculture and Rural Development. Investment by the government and by international partners for rabies prevention and control has played a substantial role in reducing human rabies deaths from 404 cases in 1992 to 74 cases in 2017. The catalyst for this effort was the Prime Minister's creation of the National Rabies Program in 1996, which led to increased support and resources for rabies prevention and control. Interventions carried out since then include the expansion of post-exposure prophylaxis centres throughout the country, the introduction or revision of key legislation and guidelines, and improved multisectoral One Health collaboration. In addition, support from international partners, such as the World Organisation for Animal Health (OIE), the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), and the Centers for Disease Control and Prevention (CDC), has helped to increase awareness, manage dog populations more effectively, and improve Vietnam's surveillance and diagnostic capabilities. To pursue the goal of eliminating dog-mediated rabies in Vietnam, political commitment is crucial. Resources must be made available to enforce the regulations and guidelines that will enable Vietnam to achieve greater canine rabies vaccination coverage. In this paper, the authors provide an overview of the animal and human health systems in Vietnam, as well as past, current and future directions of rabies prevention and control.

La rage est une maladie virale à l'issue mortelle faisant chaque année un nombre estimé de 59 000 victimes humaines. La plupart de ces décès surviennent dans les pays en développement d'Asie. Au Vietnam, la rage canine est endémique mais le pays poursuit activement l'objectif d'éliminer la rage de son territoire. À l'instar du Vietnam, plusieurs pays ont investi des ressources colossales pour contrôler la rage, renforçant ainsi la dimension régionale et mondiale de l'objectif d'élimination de cette maladie négligée. Au Vietnam, la rage figure parmi les cinq zoonoses hautement prioritaires prises en compte par le ministère de la Santé et le ministère de l'Agriculture et du développement rural. Les investissements consacrés à la prévention et au contrôle de la rage par le gouvernement et ses partenaires internationaux ont joué un rôle déterminant dans la réduction du nombre de décès humains dus à la rage, qui est passé de 404 cas en 1992 à 74 cas en 2017. L'élément catalyseur de cet effort a été la création en 1996 du Programme national de lutte contre la rage par le premier ministre de l'époque, ce qui a permis de renforcer les ressources et le soutien dédiés à la prévention et à la lutte contre la rage. Depuis lors, les interventions ont porté sur la création de centres de prophylaxie post-exposition sur tout le territoire, l'introduction ou la révision de la législation et des lignes directrices applicables et l'amélioration de la collaboration Une seule santé. En outre, le soutien de partenaires internationaux tels que l'Organisation mondiale de la santé animale (OIE), l'Organisation mondiale de la santé (OMS), l'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO) et les Centres pour le contrôle et la prévention des maladies (CDC, États-Unis d'Amérique) a abouti à une meilleure sensibilisation, à une gestion plus efficace des populations de chiens et à un renforcement des capacités de surveillance et de diagnostic au Vietnam. Un engagement politique fort est indispensable pour réussir à éliminer totalement la rage transmise par les chiens au Vietnam. Des ressources doivent être rendues disponibles afin de mettre en oeuvre la réglementation et les lignes directrices pertinentes et d'augmenter ainsi la couverture vaccinale de la population canine du pays. Les auteurs décrivent les systèmes de santé animale et publique du Vietnam ainsi que les orientations passées, actuelles et futures de la prévention et du contrôle de la rage dans le pays.

La rabia es una enfermedad vírica fatal, que según las estimaciones mata a 59 000 personas al año, mayoritariamente en países en desarrollo asiáticos. La rabia canina es endémica en el Vietnam, país que no obstante avanza ahora hacia la eliminación de la enfermedad. Como el Vietnam, muchos países han invertido cantidades colosales de recursos en la lucha antirrábica, subrayando con ello su compromiso con el objetivo de eliminar esta enfermedad desatendida a escala regional y mundial. El Ministerio de Salud y el Ministerio de Agricultura y Desarrollo Rural del Vietnam tienen catalogada la rabia como una de las cinco enfermedades zoonóticas que revisten máxima prioridad. Las inversiones en prevención y control de la rabia realizadas por el gobierno y por asociados internacionales han ayudado sensiblemente a reducir el número de personas muertas por la rabia, que ha pasado de 404 casos en 1992 a 74 en 2017. El catalizador de este esfuerzo fue la creación en 1996, por iniciativa del Primer Ministro, del Programa Nacional contra la Rabia, que se tradujo en un aumento del apoyo y los recursos destinados a prevenir y combatir la enfermedad. Entre otras intervenciones, desde entonces se ha multiplicado en todo el país el número de centros donde se dispensa profilaxis tras la exposición, se han promulgado o revisado leyes, decretos y directrices fundamentales y se ha mejorado la colaboración multisectorial en clave de Una sola salud. Además, el respaldo de asociados internacionales como la Organización Mundial de Sanidad Animal (OIE), la Organización Mundial de la Salud (OMS), la Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO) o los Centros para el Control y la Prevención de Enfermedades (CDC) de los Estados Unidos ha ayudado a generar una mayor conciencia del problema, a gestionar más eficazmente las poblaciones de perros y a dotar al país de mejores medios de vigilancia y diagnóstico. Para hacer realidad el objetivo de eliminar del Vietnam la rabia transmitida por perros, la voluntad política es un factor clave, pues hay que poner sobre la mesa los recursos necesarios para aplicar los reglamentos y normas que permitirán al país ampliar la cobertura de vacunación canina antirrábica. Tras trazar una panorámica de los sistemas sanitario y zoosanitario del Vietnam, los autores describen el rumbo pasado, presente y futuro de las labores de prevención y control de la rabia en el país.

Encapsulation of Neurotoxins, Blockers of Nicotinic Acetylcholine Receptors, in Nanomaterials Based on Sulfated Polysaccharides.

Three-finger snake neurotoxins are selective antagonists of some nicotinic acetylcholine receptor subtypes and are widely used to study these receptors. The peptide neurotoxin azemiopsin, recently isolated from the venom of Azemipos feae, is a selective blocker of muscle-type nicotinic acetylcholine receptor. In order to reduce their toxicity and increase resistance under physiological conditions, we have encapsulated these toxins into nanomaterials. The study of nanomaterials after interaction with neurotoxins by the methods of transmission electron microscopy and dynamic light scattering revealed an increase in the size of nanoparticles, which indicates the inclusion of neurotoxins in nanomaterials.

Correction to: Common findings of blaCTX-M-55-encoding 104-139 kbp plasmids harbored by extended-spectrum ß-lactamase-producing Escherichia coli in pork meat, wholesale market workers, and patients with urinary tract infection in Vietnam.

The original version of this article unfortunately contained a mistake. The legends of Tables 2 and 3, Fig. 1 are incorrect. The corrected legends are given below.

The Effect of Freezing Time on Muscle Fiber Mechanical Properties.

The purpose of this study was to investigate the effect of freezing time on the functional behavior of mouse muscle fibers. Passive mechanical tests were performed on single soleus muscle fibers from fresh (0 month) and preserved (stored at -20°C for 3, 6, 9 and 12 months) 3 month old mice. The Young's modulus and the dynamic and the static stresses were measured. A viscoelastic Hill model of 3rd order was used to fit the experimental relaxation test data. The statistical analysis corresponding to the elastic modulus of single muscle fibers did not differ when comparing fresh and stored samples for 3 and 6 months at -20 °C. From 9 months, fibers were less resistant and the mechanical properties were damaged. The primary goal of this study was to complete the gold standard process of muscle fiber preservation for subsequent mechanical property studies. We have demonstrated that muscle fibers can be stored at -20°C for up to 6 months without altering their mechanical properties.