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Abstract Background Precise genetic modifications are preferred products of CRISPR-Cas9 mediated gene editing in mammalian cells but require the repair of induced double-strand breaks (DSB) through homology directed repair (HDR). Since HDR competes with the prevailing non-homologous end joining (NHEJ) pathway and depends on the presence of repair templates its efficiency is often limited and demands optimized methodology. Results For the enhancement of HDR we redirect the DSB repair pathway choice by targeting the Ubiquitin mark for damaged chromatin at Histone H2A-K15. We used fusions of the Ubiquitin binding domain (UBD) of Rad18 or RNF169 with BRCA1 to promote HDR initiation and UBD fusions with DNA binding domains to attract donor templates and facilitate HDR processing. Using a traffic light reporter system in human HEK293 cells we found that the coexpression of both types of UBD fusion proteins promotes HDR, reduces NHEJ and shifts the HDR/NHEJ balance up to 6-fold. The HDR enhancing effect of UBD fusion proteins was confirmed at multiple endogenous loci. Conclusions Our findings provide a novel efficient approach to promote precise gene editing in human cells. more...

In the extant literature either income or consumption expenditures as measured over short periods of time have been regarded as a proxy for the material well-being of households. However, economists have long recognized that a household's sense of well-being depends not just on its average income or expenditures, but also on the risks it faces and its ability to deal with these risks. Hence vulnerability is a more satisfactory measure of welfare. In this study we used the concept of vulnerability as expected poverty to assess the household vulnerability to poverty in four Central Asian countries: Azerbaijan, Kazakhstan, Kyrgyzstan, and Tajikistan. Except for Tajikistan, headcount poverty and vulnerability rates are significantly different. We also find that vulnerability differs significantly across households by location and selected household characteristics. In this paper we use a simple empirical measurement that allows estimating the headcount vulnerability to poverty using cross-section data. This measurement is based on the strong assumption that households have the same conditional distribution of consumption in a stationary environment. While this approach cannot capture all dimensions of vulnerability, it at least begins to raise the policy issue that vulnerability should be considered alongside poverty. more...

This study employed novel extraction methods with natural deep eutectic solvents (NADES) to extract bioactive compounds and proteins from Bacopa monnieri leaves. The conditional influence of ultrasonic-assisted extraction (UAE), microwave-assisted extraction (MAE), and enzymatic-assisted extraction (EAE) on the recovery efficiency of phenolics, proteins, flavonoids, and terpenoids was evaluated. The conditions of UAE were 50 mL/g LSR, 600W of ultrasonic power, and 30% water content with 40°C for 1 min to obtain the highest bioactive compounds and protein contents. The conditions of MAE were 40 mL/g LSR, 400W of microwave power with 30% water content for 3 min to reach the highest contents of biological compounds. The conditions of EAE were 30 mL/g of LSR, 20 U/g of enzyme concentration with L-Gly-Na molar ratio at 2:4:1, and 40% water content for 60 min to acquire the highest bioactive compound contents. Scanning electron microscopy (SEM) is employed to analyze the surface of Bacopa monnieri leaves before and after extraction. Comparing seven extraction methods was conducted to find the most favorable ones. The result showed that the UMEAE method was the most effective way to exploit the compounds. The study suggested that UMEAE effectively extracts phenolics, flavonoids, terpenoids, and protein from DBMP. more...

The Tien Giang province is located in the tropical climate zone of the Mekong delta. In this study, the diversity of zooplankton and benthic macroinvertebrates were investigated in the estuarine coastal waters of the Tien Giang province of southern Vietnam. 10 sites were observed over six time periods from 2019 (March, May, September, and November) and 2020 (March and May). The taxonomic richness, abundance, and diversity index were applied to this biodiversity assessment of the zooplankton and benthic macroinvertebrates. The results of the assessment showed that 30 species of zooplankton and 18 species of benthic macroinvertebrates were found in the study area. The density of zooplankton at each site ranged from 6 to 93 individuals/sample, while the density of benthic macroinvertebrates at each site fluctuated from 3 to 12 individuals/sample. The Shannon-Wiener diversity index of zooplankton fluctuated from 1.02 to 1.58 and that of the benthic macroinvertebrates ranged between 0.91 and 1.33. Besides, statistical analysis showed that the species richness of the zooplankton and benthic macroinvertebrates positively correlated with their density (r=0.2283-0.6423). This study contributes to the diversity information of zooplankton and benthic macroinvertebrates, which can be used to position the sustainable management of natural resources and evaluate the natural feed sources for aquaculture in this estuarine area. more...

DYT1 early-onset generalized dystonia is a hyperkinetic movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Recently, significant progress has been made in studying pathophysiology of DYT1 dystonia using targeted mouse models. Dyt1 ΔGAG heterozygous knock-in (KI) and Dyt1 knock-down (KD) mice exhibit motor deficits and alterations of striatal dopamine metabolisms, while Dyt1 knockout (KO) and Dyt1 ΔGAG homozygous KI mice show abnormal nuclear envelopes and neonatal lethality. However, it has not been clear whether motor deficits and striatal abnormality are caused by Dyt1 mutation in the striatum itself or the end results of abnormal signals from other brain regions. To identify the brain region that contributes to these phenotypes, we made a striatum-specific Dyt1 conditional knockout (Dyt1 sKO) mouse. Dyt1 sKO mice exhibited motor deficits and reduced striatal dopamine receptor 2 (D2R) binding activity, whereas they did not exhibit significant alteration of striatal monoamine contents. Furthermore, we also found normal nuclear envelope structure in striatal medium spiny neurons (MSNs) of an adult Dyt1 sKO mouse and cerebral cortical neurons in cerebral cortex-specific Dyt1 conditional knockout (Dyt1 cKO) mice. The results suggest that the loss of striatal torsinA alone is sufficient to produce motor deficits, and that this effect may be mediated, at least in part, through changes in D2R function in the basal ganglia circuit. more...

A new diterpenoid, phyllane C (1), along with three known compounds, ovoideal E (2), spruceanol (3), and fluacinoid B (4) were isolated from the leaves of Phyllanthus acidus growing in Thailand. The structures were determined by analysis of their MS and NMR data as well as by comparison with literature values. DFT-NMR chemical shift calculations and subsequent DP4/DP4+ probability methods were applied to define the relative configuration of 1. Compound 3 showed a weak cytotoxicity against K562 cell line (IC50 41.9 ± 2.31 µg/mL). [ABSTRACT FROM AUTHOR] more...

Background: According to the International Diabetes Federation, total global health care expenditures for diabetes tripled between 2003 and 2013 because of increases in the number of people with diabetes as well as in the average expenditures per patient. This study aims to provide accurate and timely information about the economic impacts of type 2 diabetes mellitus (T2DM) in Vietnam. Method: The cost-of-illness estimates followed a prospective, prevalence-based approach from the societal perspective of T2DM with 392 selected diabetic patients who received treatment from a public hospital in Ho Chi Minh City, Vietnam, during the 2016 fiscal year. Results: In this study, the annual cost per patient estimate was US $246.10 (95% CI 228.3, 267.2) for 392 patients, which accounted for about 12% (95% CI 11, 13) of the gross domestic product per capita in 2017. That includes US $127.30, US $34.40 and US $84.40 for direct medical costs, direct nonmedical expenditures, and indirect costs, respectively. The cost of pharmaceuticals accounted for the bulk of total expenditures in our study (27.5% of total costs and 53.2% of direct medical costs). A bootstrap analysis showed that female patients had a higher cost of treatment than men at US $48.90 (95% CI 3.1, 95.0); those who received insulin and oral antidiabetics (OAD) also had a statistically significant higher cost of treatment compared to those receiving OAD, US $445.90 (95% CI 181.2, 690.6). The Gradient Boosting Regression (Ensemble method) and Lasso Regression (Generalized Linear Models) were determined to be the best models to predict the cost of T2DM (R2=65.3, mean square error [MSE]=0.94; and R2=64.75, MSE=0.96, respectively). Conclusion: The findings of this study serve as a reference for policy decision making in diabetes management as well as adjustment of costs for patients in order to reduce the economic impact of the disease. [ABSTRACT FROM AUTHOR] more...

This paper uses cross-section data from the 1996 Papua New Guinea Household Survey to assess household vulnerability to poverty in Papua New Guinea. Vulnerability varies across regions, household size, gender and level of education of households. We use a simple empirical model that permits estimation of vulnerability to poverty assuming that households have the same conditional distribution of consumption in a stationary environment. Although this approach does not capture all dimensions of vulnerability, it at least raises the policy interest that vulnerability should be considered alongside poverty. [ABSTRACT FROM AUTHOR] more...

DYT1 dystonia is a primary generalized early-onset torsion dystonia caused by mutations in DYT1 that codes for torsinA and has an autosomal dominant inheritance pattern with ∼30% penetrance. Abnormal activity in the pallidal–thalamic–cortical circuit, especially in the globus pallidus internus, is the proposed cause of dystonic symptoms. However, recent neuroimaging studies suggest significant contribution of the cerebral cortex. To understand the contribution of the cerebral cortex to dystonia, we produced cerebral cortex-specific Dyt1 conditional knockout mice and analysed their behaviour. The conditional knockout mice exhibited motor deficits and hyperactivity that mimic the reported behavioural deficits in Dyt1 ΔGAG knockin heterozygous and Dyt1 knockdown mice. Although the latter two mice exhibit lower levels of dopamine metabolites in the striatum, the conditional knockout mice did not show significant alterations in the striatal dopamine and its metabolites levels. The conditional knockout mice had well-developed whisker-related patterns in somatosensory cortex, suggesting formations of synapses and neural circuits were largely unaffected. The results suggest that the loss of torsinA function in the cerebral cortex alone is sufficient to induce behavioural deficits associated with Dyt1 ΔGAG knockin mutation. Developing drugs targeting the cerebral cortex may produce novel medical treatments for DYT1 dystonia patients. [ABSTRACT FROM PUBLISHER] more...

Mutations of ɛ-sarcoglycan gene (SGCE) have been implicated in myoclonus-dystonia (M-D), a movement disorder. To determine the pathophysiology of M-D, we produced Sgce knockout mice and found that the knockout mice exhibited myoclonus, motor impairments, hyperactivity, anxiety, depression, significantly higher levels of striatal dopamine and its metabolites, and an inverse correlation between the dopamine and serotonin metabolites. The results suggest that the diverse symptoms associated with M-D are indeed resulted from a single SGCE gene mutation that leads to alterations of dopaminergic and serotonergic systems. Therefore, antipsychotic agents and serotonin reuptake inhibitors may offer potential benefits for M-D patients. [ABSTRACT FROM PUBLISHER] more...

DYT-TOR1A or DYT1 early-onset generalized dystonia is an inherited movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, or abnormal postures. The majority of the DYT1 dystonia patients have a trinucleotide GAG deletion in DYT1/TOR1A. Trihexyphenidyl (THP), an antagonist for excitatory muscarinic acetylcholine receptor M1, is commonly used to treat dystonia. Dyt1 heterozygous ΔGAG knock-in (KI) mice, which have the corresponding mutation, exhibit impaired motor-skill transfer. Here, the effect of THP injection during the treadmill training period on the motor-skill transfer to the accelerated rotarod performance was examined. THP treatment reversed the motor-skill transfer impairment in Dyt1 KI mice. Immunohistochemistry showed that Dyt1 KI mice had a significant reduction of the dorsolateral striatal cholinergic interneurons. In contrast, Western blot analysis showed no significant alteration in the expression levels of the striatal enzymes and transporters involved in the acetylcholine metabolism. The results suggest a functional alteration of the cholinergic system underlying the impairment of motor-skill transfer and the pathogenesis of DYT1 dystonia. Training with THP in a motor task may improve another motor skill performance in DYT1 dystonia. more...

Background and challenges to implementation Almost 16 million Vietnamese adults currently smoke tobacco, including 45.3% of men and 1.1% of women. In Vietnam more women die from tobacco-related disease (9.5%) than smoke cigarettes, suggesting that women suffer disproportionately greater illness and premature death from exposure to secondhand smoke (SHS). Intervention or response The Vietnam Women's Union developed the “Women create smoke-free homes” national initiative to help protect women and children from exposure to SHS throughout Vietnam. Supported by Vital Strategies and Danson Media, a campaign was designed for the initiative, featuring the personal story of a 41 year-old, non-smoking victim of lung cancer, Ms Nguyen Thi Huong, with a call to action to “Protect yourselves and your loved ones”. Pre-testing research was conducted on initial testimonial edits to strengthen communication of Ms Huong's story. The resulting three 30-second ads were launched by the Women´s Union and disseminated from December 2016 to February 2017 through Facebook, with accompanying Facebook posts, radio spots and public relations activities in print, online, radio and television media. Results and lessons learnt The testimonial ads received 4,152,937 views, with Facebook comments mostly from women tagging male partners. A national tobacco campaign evaluation study (n=2022) found 8% of respondents, including 10% of female non-smoker respondents, recalled the testimonial ads unprompted (representing approximately 4.75 million people aged 15-55 years). Of these, 74% of female non-smokers (and 75% of male smokers) reported trying to make their home 'smokefree' and 77% reported trying to persuade others to quit smoking as a result of seeing the ads, while 67% of male smokers reported making a quit attempt after seeing the ads. Conclusions and key recommendations The campaign demonstrates effectiveness of a national Women's Organization communicating personal stories of tobacco-related harm to women. This supports previous evidence of the power of testimonial approaches and points to further potential opportunities for tobacco control communication in Vietnam and other countries. more...

DYT1 dystonia is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most of the patients have a trinucleotide deletion (ΔGAG) corresponding to a glutamic acid in the C-terminal region (torsinA(ΔE)). Dyt1 ΔGAG heterozygous knock-in (KI) mice, which mimic ΔGAG mutation in the endogenous gene, exhibit motor deficits and deceased frequency of spontaneous excitatory post-synaptic currents (sEPSCs) and normal theta-burst-induced long-term potentiation (LTP) in the hippocampal CA1 region. Although Dyt1 KI mice show decreased hippocampal torsinA levels, it is not clear whether the decreased torsinA level itself affects the synaptic plasticity or torsinA(ΔE) does it. To analyze the effect of partial torsinA loss on motor behaviors and synaptic transmission, Dyt1 heterozygous knock-out (KO) mice were examined as a model of a frame-shift DYT1 mutation in patients. Consistent with Dyt1 KI mice, Dyt1 heterozygous KO mice showed motor deficits in the beam-walking test. Dyt1 heterozygous KO mice showed decreased hippocampal torsinA levels lower than those in Dyt1 KI mice. Reduced sEPSCs and normal miniature excitatory post-synaptic currents (mEPSCs) were also observed in the acute hippocampal brain slices from Dyt1 heterozygous KO mice, suggesting that the partial loss of torsinA function in Dyt1 KI mice causes action potential-dependent neurotransmitter release deficits. On the other hand, Dyt1 heterozygous KO mice showed enhanced hippocampal LTP, normal input-output relations and paired pulse ratios in the extracellular field recordings. The results suggest that maintaining an appropriate torsinA level is important to sustain normal motor performance, synaptic transmission and plasticity. Developing therapeutics to restore a normal torsinA level may help to prevent and treat the symptoms in DYT1 dystonia. more...

Hydrogen bonds (H-bonds) in the complexes between aldehydes and hydrogen chalcogenides, XCHO... n H 2 Z with X = H, F, Cl, Br, and CH 3 , Z = O, S, Se, and Te, and n = 1,2, were investigated using high-level ab initio calculations. The C sp2 -H...O H-bonds are found to be about twice as strong as the C sp2 -H...S/Se/Te counterparts. Remarkably, the S/Se/Te-H...S/Se/Te H-bonds are 4.5 times as weak as the O-H...O ones. The addition of the second H 2 Z molecule into binary systems induces stronger complexes and causes a positive cooperative effect in ternary complexes. The blue shift of C sp2 -H stretching frequency involving the C sp2 -H...Z H-bond sharply increases when replacing one H atom in HCHO by a CH 3 group. In contrast, when one H atom in HCHO is substituted with a halogen, the magnitude of blue-shifting of the C sp2 -H...Z H-bond becomes smaller. The largest blue shift up to 92 cm -1 of C sp2 -H stretching frequency in C sp2 -H...O H-bond in CH 3 CHO...2H 2 O has rarely been observed and is much greater than that in the cases of the C sp2 -H...S/Se/Te ones. The C sp2 -H blue shift of C sp2 -H...Z bonds in the halogenated aldehydes is converted into a red shift when H 2 O is replaced by a heavier analogue, such as H 2 S, H 2 Se, or H 2 Te. The stability and classification of nonconventional H-bonds including C sp2 -H...Se/Te, Te-H...Te, and Se/Te-H...O have been established for the first time. more...

A pentagonal hetero-prismatic structural motif was found for singly transition metal doped M@Ge 5 E 5 + clusters, where the transition metal atom is located at the centre of a (5/5) Ge 5 E 5 prism in which Ge is mixed with either P or As atoms. Structural characterization indicates that each (5/5) Ge 5 E 5 prism is established by joining of two Ge 3 E 2 and Ge 2 E 3 strings in a prismatic fashion rather than two Ge 5 and E 5 strings. Each string results from a remarkable mixture of Ge and E atoms and contains only one E-E connection due to the fact that Ge-E bonds are much stronger than E-E connections. From the donor-acceptor perspective, the Ge 5 E 5 tube donates electrons to the M center, which behaves as an acceptor. NBO atomic charge and ELI_D analyses demonstrate such electrostatic interactions of the M dopant with a Ge 5 E 5 + tube which likely induce thermodynamic stability for the resulting M@Ge 5 E 5 + cluster. CMO analysis illustrates that the conventional 18 electron count is recovered in the M@Ge 5 E 5 + cations., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.) more...

Background: Dengue is a mosquito-borne viral illness with the world's fastest rate of infection. In 2014, Vietnam had recorded 43,000 cases in 53 provinces, with 28 deaths., Materials and Methods: A 6-month cross-sectional study was conducted from September 2015 to March 2016 at Cu Chi General Hospital. Cost of illness in this study was estimated under the incidence-based approach from the societal perspective., Results: The average cost per case was US$139.3±$61.7. The average cost per child was higher than per adult, but not significant ($151.0±$63.5 and $132.7±$59.9, respectively; P =0.068). Meanwhile, 50.2% of the total cost was contributed by the cost of hospital bed. According to the sensitivity analysis, if both the costs of the hospital bed and ultrasound were reduced by 10%, the total treatment cost of dengue fever would fall by 5% and 1.6%, respectively., Conclusion: This study is expected to be the basis for investment-plan formulation and fund allocation for the treatment and prevention of dengue. In an attempt to examine the entire socioeconomic encumbrance caused by the dengue virus, a larger scale study targeting both dengue and dengue hemorrhagic fever needs to be conducted in several hospitals., Competing Interests: The authors report no conflicts of interest in this work. more...