Customizable Porphyrin Platform Enables Folate Receptor PET Imaging Using Copper-64.

Folate receptors including folate receptor α (FRα) are overexpressed in up to 90% of ovarian cancers. Ovarian cancers overexpressing FRα often exhibit high degrees of drug resistance and poor outcomes. A porphyrin chassis has been developed that is readily customizable according to the desired targeting properties. Thus, compound O5 includes a free base porphyrin, two water-solubilizing groups that project above and below the macrocycle plane, and a folate targeting moiety. Compound O5 was synthesized (>95% purity) and exhibited aqueous solubility of at least 0.48 mM (1 mg/mL). Radiolabeling of O5 with 64Cu in HEPES buffer at 37 °C gave a molar activity of 1000 µCi/µg (88 MBq/nmol). [64Cu]Cu-O5 was stable in human serum for 24 h. Cell uptake studies showed 535 ± 12% bound/mg [64Cu]Cu-O5 in FRα-positive IGROV1 cells when incubated at 0.04 nM. Subcellular fractionation showed that most radioactivity was associated with the cytoplasmic (39.4 ± 2.7%) and chromatin-bound nuclear (53.0 ± 4.2%) fractions. In mice bearing IGROV1 xenografts, PET imaging studies showed clear tumor uptake of [64Cu]Cu-O5 from 1 to 24 h post injection with a low degree of liver uptake. The tumor standardized uptake value at 24 h post injection was 0.34 ± 0.16 versus 0.06 ± 0.07 in the blocking group. In summary, [64Cu]Cu-O5 was synthesized at high molar activity, was stable in serum, exhibited high binding to FRα-overexpressing cells with high nuclear translocation, and gave uptake that was clearly visible in mouse tumor xenografts.

Tethered Indoxyl-Glucuronides for Enzymatically Triggered Cross-Linking.

Indoxyl-glucuronides, upon treatment with ß-glucuronidase under physiological conditions, are well known to afford the corresponding indigoid dye via oxidative dimerization. Here, seven indoxyl-glucuronide target compounds have been prepared along with 22 intermediates. Of the target compounds, four contain a conjugatable handle (azido-PEG, hydroxy-PEG, or BCN) attached to the indoxyl moiety, while three are isomers that include a PEG-ethynyl group at the 5-, 6-, or 7-position. All seven target compounds have been examined in indigoid-forming reactions upon treatment with ß-glucuronidase from two different sources and rat liver tritosomes. Taken together, the results suggest the utility of tethered indoxyl-glucuronides for use in bioconjugation chemistry with a chromogenic readout under physiological conditions.

Chicken infectious anaemia virus infections in chickens in northern Vietnam: epidemiological features and genetic characterization of the causative agent.

Since the first report of chicken infectious anaemia virus (CIAV) in Vietnam in 2013, there have not been many studies focused on the detection of CIAV or the molecular characteristics of the virus. This study attempted to investigate the presence of CIAV in northern Vietnam by molecular-based methods. Regarding the spatial distribution of CIAV, the PCR-based results showed that CIAV was detected in 47 out of 64 farms (73.4%) and in all 10 investigated provinces. Of the 119 samples assayed by PCR, 74 (62.2%) tested positive for CIAV DNA. By arranging the samples into different categories, it was found that CIAV was detected at high rates (above 50%) based on all 4 evaluated criteria as follows: production type of chicken, housing system, flock size and age group. Different housing systems were significantly associated with the detection rates of CIAV (P = 0.003). By genetic analyses, all of the Vietnamese CIAVs were found to (i) lack substitutions related to attenuation substitutions, (ii) group separately from vaccine-like CIAVs and (iii) belong to genogroups G2 and G3 of CIAV. Because of the wide distribution of CIAV and because the virus was confirmed not to be vaccine-like viruses, it is suggested that further studies be conducted on the clinical form of chicken infectious anaemia, as well as the immunosuppressive effect of CIAV on chickens in Vietnam.RESEARCH HIGHLIGHTS Wide distribution of chicken infectious anaemia virus (CIAV) in northern Vietnam.Vietnamese CIAVs belong to genogroups G2 and G3 of CIAV.

Return spillover of Vietnam's sectors in response to US uncertainties.

This paper investigates the impact of US economic policy uncertainty and geopolitical risk on the return spillovers among 24 sectors in Vietnam from April 13, 2017, to April 8, 2022. The VAR-based connectedness approach and quantile techniques are employed in this study. Empirical results from the study reveal that an increase in US economic policy uncertainty significantly impacts return spillovers. However, this impact is only observed during periods of heightened uncertainty in US economic policy. Economic policy uncertainty plays a more prominent role in affecting the spillovers across Vietnamese sectors compared to geopolitical risk. Findings from our analysis also highlight the crucial role of the banking sector as a transmitter of risk in the Vietnamese stock market.

Design of a Configurable 16-Electrode Sense and Stimulation Neuromodulation System.

Electrical sensing and stimulation of nervous system activity is a valuable tool to investigate neural activity both in vivo and in vitro. A general system capable of supporting users across a variety of use cases would be valuable for the field of neuroscience. We propose a new system capable of supporting a variety of experimental cases including low and high impedance electrodes with stimulation amplitudes up to multiple mA. The system is designed to support sampling frequencies up to 26 kHz and to maximize stimulation flexibility with an electrically isolated system.

De novo variants of dominant monogenic disorders in Vietnam detected by a noninvasive prenatal test: a case series.

Background: Noninvasive prenatal tests for monogenic diseases (NIPT-SGG) have recently been reported as helpful in early-stage antenatal screening. Our study describes the clinical and genetic features of cases identified by NIPT-SGG. Materials & methods: In a cohort pregnancy with abnormal sonograms, affected cases were confirmed by invasive diagnostic tests concurrently, with NIPT-SGG targeting 25 common dominant single-gene diseases. Results: A total of 13 single-gene fetuses were confirmed, including Noonan and Costello syndromes, thanatophoric dysplasia, achondroplasia, osteogenesis imperfecta and Apert syndrome. Two novel variants seen were tuberous sclerosis complex (TSC2 c.4154G>A) and Alagille syndrome (JAG1 c.3452del). Conclusion: NIPT-SGG and standard tests agree on the results for 13 fetuses with monogenic disorders. This panel method of screening can benefit high-risk Vietnamese pregnancies, but further research is encouraged to expand on the causative gene panel.

Developing and validating noninvasive prenatal testing for de novo autosomal dominant monogenic diseases in Vietnam.

Background: Over 60% of single-gene diseases in newborns are autosomal dominant variants. Noninvasive prenatal testing for monogenic conditions (NIPT-SGG) is cost-effective and timesaving, but not widely applied. This study introduces and validates NIPT-SGG in detecting 25 monogenic conditions. Methods: NIPT-SGG with a 30-gene panel applied next-generation sequencing and trio assays to confirm de novo variants. Diagnostic tests confirmed NIPT-detected cases. Results: Among 93 pregnancies with ultrasound findings, 11 (11.8%) fetuses were screened and diagnosed with monogenic diseases, mostly with Noonan syndrome. NIPT-SGG determined >99.99% of actual positive and negative cases, confirmed by diagnostic tests. No false-negatives or false-positives were reported. Conclusion: NIPT-SGG effectively identifies the fetuses affected with monogenic diseases, which is a promisingly safe and timely antenatal screening option for high-risk pregnancies.

Fall Prediction in People with Parkinson's Disease.

A preliminary study result predicting fall events in patients with Parkinson's disease (PD) by using a simple motion sensor is described in this paper. Causes of falls in people with PD can be postural instability, freezing of gait, festinating gait, dyskinesias, visuospatial dysfunction, orthostatic hypotension, and posture problems. This study uses only one motion sensor in collecting data. Thus, only fall events caused by festinating gait factors, which are moments when the patient suddenly moves faster with smaller steps, can be performed and tested. In this preliminary study, fall event scenarios of simulated test cases are performed by five healthy young subjects aged 20 to 28 years old. The acceleration mode in the motion sensor provides information that can detect how fast the subjects move. Data collected by the sensor will be analyzed by simple analysis methods and machine learning techniques classification. The proposed study achieved an accuracy of 70.3% for the 10-class model, while for binary classification, the accuracy was 99%. Clinical Relevance-This study focuses on predicting falls by analyzing the gaits prior to an actual so that fall prediction can be possible. If falls can be predicted, researchers can develop other protective gear to prevent fall-related injuries not only for PD patients but also for the elderly.

Biochemical characterization of a recombinant acid phosphatase from Acinetobacter baumannii.

Genomic sequence analysis of Acinetobacter baumannii revealed the presence of a putative Acid Phosphatase (AcpA; EC 3.1.3.2). A plasmid construct was made, and recombinant protein (rAcpA) was expressed in E. coli. PAGE analysis (carried out under denaturing/reducing conditions) of nickel-affinity purified protein revealed the presence of a near-homogeneous band of approximately 37 kDa. The identity of the 37 kDa species was verified as rAcpA by proteomic analysis with a molecular mass of 34.6 kDa from the deduced sequence. The dependence of substrate hydrolysis on pH was broad with an optimum observed at 6.0. Kinetic analysis revealed relatively high affinity for PNPP (Km = 90 µM) with Vmax, kcat, and Kcat/Km values of 19.2 pmoles s-1, 4.80 s-1(calculated on the basis of 37 kDa), and 5.30 x 104 M-1s-1, respectively. Sensitivity to a variety of reagents, i.e., detergents, reducing, and chelating agents as well as classic acid phosphatase inhibitors was examined in addition to assessment of hydrolysis of a number of phosphorylated compounds. Removal of phosphate from different phosphorylated compounds is supportive of broad, i.e., 'nonspecific' substrate specificity; although, the enzyme appears to prefer phosphotyrosine and/or peptides containing phosphotyrosine in comparison to serine and threonine. Examination of the primary sequence indicated the absence of signature sequences characteristic of Type A, B, and C nonspecific bacterial acid phosphatases.

Choline chloride-based deep eutectic solvents as effective electrolytes for dye-sensitized solar cells.

Electrolytes for dye-sensitized solar cells remain a challenge for large-scale production and commercialization, hindering the wide application of solar cells. We have developed two new electrolyte-based deep eutectic solvents using a mixture of choline chloride with urea and with ethylene glycol for dye-sensitized solar cells. The prominent features of the two deep eutectic solvent electrolytes are simple preparation for large-scale production with inexpensive, available, and nontoxic starting materials and biodegradability. The solar cell devices proceeded in a safe manner as the two deep eutectic solvents afforded low-cost technology and comparative conversion efficiency to a popular ionic liquid, namely 1-ethyl-3-methylimidazolium tetracyanoborate. Results showed that devices with choline chloride and urea electrolyte exhibited improved open circuit voltage values (V OC), while the ones with choline chloride and ethylene glycol showed an increase in the short circuit current (I sc). Characterization of the devices by electrochemical impedance spectroscopy helped explain the effects of their molecular structures on the enhancement of either V OC or I sc values. These new solvents expand the electrolyte choices for designing dye-sensitized solar cells, especially for the purpose of using low-cost and eco-friendly materials for massive production.

Myocardial Infarction Complications After Surgery in Vietnam: Estimates of Incremental Cost, Readmission Risk, and Length of Hospital Stay.

Myocardial infarction is a considerable burden on public health. However, there is a lack of information about its economic impact on both the individual and national levels. This study aims to estimate the incremental cost, readmission risk, and length of hospital stay due to myocardial infarction as a post-operative complication. We used data from a standardized national system managed by the Vietnam Social Insurance database. The original sample size was 1,241,893 surgical patients who had undergone one of seven types of surgery. A propensity score matching method was applied to create a matched sample for cost analysis. A generalized linear model was used to estimate direct treatment costs, the length of stay, and the effect of the complication on the readmission of surgical patients. Myocardial infarction occurs most frequently after vascular surgery. Patients with a myocardial infarction complication were more likely to experience readmission within 30 and 90 days, with an OR of 3.45 (95%CI: 2.92-4.08) and 4.39 (95%CI: 3.78-5.10), respectively. The increments of total costs at 30 and 90 days due to post-operative myocardial infarction were 4,490.9 USD (95%CI: 3882.3-5099.5) and 4,724.6 USD (95%CI: 4111.5-5337.8) per case, while the increases in length of stay were 4.9 (95%CI: 3.6-6.2) and 5.7 (95%CI: 4.2-7.2) per case, respectively. Perioperative myocardial infarction contributes significantly to medical costs for the individual and the national economy. Patients with perioperative myocardial infarction are more likely to be readmitted and face a longer treatment duration.

The effect of adverse childhood experiences on depression, psychological distress and suicidal thought in Vietnamese adolescents: Findings from multiple cross-sectional studies.

Exposing to adverse childhood experiences (ACEs) has been identified as one of the major contributing factors to poor mental health and suicide in adolescents. However, little is known about this relationship in Vietnamese adolescents. This study aimed to evaluate the effect of ACEs on depression, psychological distress and suicidal thought among Vietnamese adolescents across different areas in Vietnam. Cross-sectional surveys were conducted among 4957 secondary school and high school students aged 13-20 in urban area, rural area, border area and mountainous area. The students were asked to complete a self-report questionnaire which included the Center for Epidemiological studies - Depression, the Kessler-10 and ACE questionnaire from the WHO Adverse Childhood Experiences Study. Suicidal thought was evaluated by a single question from the U.S. Youth Risk Behavior Survey. Among 4720 students included in the analysis, 54.4% were female. The prevalence of depression, psychological distress and suicidal thought was 22.9%, 30.6% and 10.9% respectively. About 86% of participants experienced at least one type of ACEs and nearly 56% reported multiple types of ACEs. Students with four or more types of ACEs had 6.98 (95% CI 5.09 -9.56), 4.72 (95 % CI 3.58-6.23) and 6.43 (95 % CI 4.45-9.30) times higher in odds of having depression, psychological distress and suicidal thought respectively. In conclusion, ACEs are common in Vietnamese adolescents and are strongly associated with depression, psychological distress and suicidal thought. Our finding indicates urgent needs for interventions targeting both ACEs and depression, psychological distress in Vietnamese adolescents.

Investigating molecular mechanism for the stability of ternary systems containing cetrimide, fatty alcohol and water by using computer simulation.

Computer simulations using atomistic model are carried out to investigate the stability of ternary systems of pure or mixed fatty alcohols, cetrimide, and water. These semi-solid oil-in-water systems are used as the main component of pharmaceutical creams. Experiments show that the mixed alcohol systems are more stable than pure ones. The current experimental hypothesis is that this is the result of the length mismatch of the alkyl chains. This leads to higher configurational entropy of the chain tip of the longer alcohol molecules. Our simulation results support this hypothesis. The magnitude in fluctuations in the area per molecule also increases in mixed systems, indicating a higher configurational entropy. Analysis of the molecular structure of simulated systems also shows good agreements with experimental data. Additionally, the results also show that the shorter alcohol molecules become stiffer with higher values of the deuterium order parameters and smaller area per molecule. This leads to more configurational space for the longer alcohol to maximize overall the free energy of the system. This is not known so far in available experimental studies of these systems.

Intracoronary Cavitation as a Cause of Plaque Rupture and Thrombosis Propagation in Patients with Acute Myocardial Infarction: A Computational Study.

BACKGROUND AND OBJECTIVES: Significant rather than moderate coronary artery stenosis has been postulated to be the main substrate of plaque rupture in acute myocardial infarction (AMI). We evaluate if cavitation could influence the coronary artery plaque rupture contributing to the progression of thrombotic process. METHODS: We reconstructed a 3D model of the left anterior descending coronary artery (LAD) after reviewing the intravascular ultrasound (IVUS) data of 30 consecutive patients with mild to severe coronary artery disease. RESULTS: Turbulent flow or cavitation occurs in both concentric and eccentric coronary artery stenosis (≥ 75% for the former and ≥ 50% for the latter). The analysis of vapor phase demonstrated that cavitation propagated downstream, creating microbubbles, which exploded when the fluid pressure was lower than the vapor pressure at a local thermodynamic state. The relative higher vorticity magnitude (as turbulent flow in vivo angiogram) observed on the distal cap of the atherosclerotic plaque created a higher turbulence, probably able to destabilize the plaque through a micro-erosion process. CONCLUSIONS: Cavitation seems to be able to promote the thrombotic occlusion within the coronary vessels due the 'constant injuries' created by the micro-explosion of bubbles.

Getting the Most: Enhancing Efficacy by Promoting Erythropoiesis and Thrombopoiesis after Gene Therapy in Mice with Hurler Syndrome.

Novel strategies are needed to solve the conundrum of achieving clinical efficacy with high vector copy numbers (VCNs) in hematopoietic stem cells (HSCs) while attempting to minimize the potential risk of oncogenesis in lentiviral vector (LV)-mediated gene therapy clinical trials. We previously reported the benefits of reprogramming erythroid-megakaryocytic (EMK) cells for high-level lysosomal enzyme production with less risk of activating oncogenes in HSCs. Herein, using a murine model of mucopolysaccharidosis type I (MPS I) with a deficiency of α-L-iduronidase (IDUA), we sought to determine the transgene minimum effective doses (MEDs) in major organs, and if a transient increase of IDUA-containing red blood cells and platelets by repeated phlebotomy would provide further therapeutic benefits in diseased mice after EMK-restricted LV-mediated gene therapy. The MEDs for complete metabolic correction ranged from 0.1 to 2 VCNs in major visceral organs, which were dramatically reduced to 0.005-0.1 VCN by one cycle of stress induction and were associated with a further reduction of pathological deficits in mice with 0.005 VCN. This work provides a proof of concept that transiently stimulating erythropoiesis and thrombopoiesis can further improve therapeutic benefits in HSC-mediated gene therapy for MPS I, a repeatable and reversible approach to enhance clinical efficacy in the treatment of lysosomal storage diseases.

Secreted luciferase for in vivo evaluation of systemic protein delivery in mice.

A naturally secreted Gaussia luciferase (Gluc) has been utilized as a reporter for bioluminescence imaging (BLI) evaluation. However, the potential application of Gluc for in vivo monitoring of systemic protein delivery, as well as its natural biodistribution, has not been studied. To examine Gluc secretion and uptake profile, we injected Gluc-encoding plasmids into mice by hydrodynamic tail-vein injection. Whole-body BLI showed that imaging quantification obtained at pawpad was directly correlated to blood Gluc activities. When gene expression was restricted to the liver by the use of a hepatic promoter, in vivo Gluc biodistribution analysis revealed the kidney/bladder, stomach/intestine, and lung as the major uptake organs. Three-dimensional BLI identified liver/stomach and lung as the main internal luminescent sources, demonstrating the feasibility of detecting major uptake organs in live animals by 3D BLI with high-background signals in circulation. Notably, Gluc levels in capillary-depleted brain samples from Gluc-injected mice were comparable to controls, suggesting that Gluc may not cross the blood-brain barrier. Gluc uptake kinetics and intracellular half-life were assessed in various types of cell lines, implicating the involvement of non-specific pinocytosis. These results suggest that Gluc-based system may provide a useful tool for in vivo evaluation of protein/agent biodistribution following systemic delivery.