Lysosomal diseases (LDs) are a group of rare inherited disorders belonging to inborn metabolism errors. LDs are characterized by the excessive storage of undegraded substrates, most often due to the enzymatic deficiency resulting from disease-causing gene variants. LDs lead to dysregulated cellular pathways and imbalanced molecular homeostasis and can affect multiple organs and tissues. Despite being rare, LDs account for a significant incidence when considered collectively. Due to complex molecular and genetic fingerprints, considerable challenges in LD management must be overcome. Diagnosis can be significantly delayed due to the broad and nonspecific clinical manifestations and the lack of specific biomarkers. Available treatments fail to fully stop the disease progression and can alter the disease's typical phenotypes with novel manifestations. Therefore, a paradigm shift is crucial to better understand LDs and provide actionable insights. Herein, we comprehensively review the literature to demonstrate that multi-omics approaches are promising for pathophysiology elucidation, biomarker discovery, and precision therapy in LDs. We recommend adopting longitudinal study designs integrated with a multi-omics-empowered framework to facilitate mechanistic delineation, biomarker discovery, and treatment development. Relevant approaches exploring the association between LDs and common neurodegenerative disorders are also discussed, paving a potential path for improved therapeutic development and ultimately improving the patient's quality of life.

The spread of tuberculosis (TB), especially multidrug-resistant TB and extensively drug-resistant TB, has strongly motivated the research and development of new anti-TB drugs. New strategies to facilitate drug combinations, including pharmacokinetics-guided dose optimization and toxicology studies of first- and second-line anti-TB drugs have also been introduced and recommended. Liquid chromatography-mass spectrometry (LC-MS) has arguably become the gold standard in the analysis of both endo- and exo-genous compounds. This technique has been applied successfully not only for therapeutic drug monitoring (TDM) but also for pharmacometabolomics analysis. TDM improves the effectiveness of treatment, reduces adverse drug reactions, and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window. Based on TDM, the dose would be optimized individually to achieve favorable outcomes. Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs, aiding in the discovery of potential biomarkers for TB diagnostics, treatment monitoring, and outcome evaluation. This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades. Besides, we discussed the advantages and disadvantages of this technique in practical use. The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted. Lastly, we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies (pharmacometrics, drug and vaccine developments, machine learning/artificial intelligence, among others) to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.

As authorities braced for the arrival of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infrastructure investments and government directives prompted action in central Viet Nam to establish capacity for genomic surveillance sequencing. From 17 November 2021 to 7 January 2022, the Pasteur Institute in Nha Trang sequenced 162 specimens from 98 150 confirmed SARS-CoV-2 cases in the region collected from 8 November to 31 December 2021. Of these, all 127 domestic cases were identified as the B.1.617.2 (Delta) variant, whereas 92% (32/35) of imported cases were identified as the B.1.1.529 (Omicron) variant, all among international flight passengers. Patients were successfully isolated, enabling health-care workers to prepare for additional cases. Most (78%) of the 32 Omicron cases were fully vaccinated, suggesting continued importance of public health and social measures to control the spread of new variants.

Background: Viet Nam confirmed its first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on 23 January 2020 among travellers from Wuhan, China, and experienced several clusters of community transmission until September. Viet Nam implemented an aggressive testing, isolation, contact tracing and quarantine strategy in response to all laboratory-confirmed cases. We report the results of SARS-CoV-2 testing during the first half of 2020 in northern Viet Nam. Methods: Between January and May 2020, 15 650 upper respiratory tract specimens were collected from 14 470 suspected cases and contacts in northern Viet Nam. All were tested for SARS-CoV-2 by real-time RT-PCR. Individuals with positive specimens were tested every three days until two tests were negative. Positive specimens from 81 individuals were cultured. Results: Among 14 470 tested individuals, 158 (1.1%) cases of SARS-CoV-2 infection were confirmed; 89 were imported and 69 were associated with community transmission. Most patients (122, 77%) had negative results after two tests, while 11 and 4 still tested positive when sampled a third and fourth time, respectively. SARS-CoV-2 was isolated from 29 of 81 specimens (36%) with a cycle threshold (Ct) value <30. Seven patients who tested positive again after testing negative had Ct values >30 and negative cultures. Conclusion Early, widespread testing for SARS-CoV-2 in northern Viet Nam identified very few cases, which, when combined with other aggressive strategies, may have dramatically contained the epidemic. We observed rapid viral clearance and very few positive results after clearance. Large-scale molecular diagnostic testing is a critical part of early detection and containment of COVID-19 in Viet Nam and will remain necessary until vaccination is widely implemented.

Ultrasonic computed tomography based on back scattering theory is the most powerful and accurate tool in ultrasound based imaging approaches because it is capable of providing quantitative information about the imaged target and detects very small targets. The duple-frequency distorted Born iterative method (DF–DBIM), which uses density information along with sound contrast for imaging, is a promising approach for imaging targets at the level of biological tissues. With two frequencies f₁ (low) and f₂ (high) through Nf₁ and Nf₂ iterations respectively, this method is used to estimate target density along with sound contrast. The implications of duple-frequency fusion for the image reconstruction quality of density information along with sound contrast based ultrasound tomography have been analyzed in this paper. In this paper, we concentrate on the selection of parameters that is supposed to be the best to improve the reconstruction quality of ultrasound tomography. When there are restraints imposed on simulated scenarios to have control of the computational cost, the iteration number Nf₁ is determined resulting in giving the best performance. The DF–DBIM is only effective if there are a moderate number of iterations, transmitters and receivers. In case that the number of transducers is either too large or too small, a result of reconstruction which is better than that of the single frequency approach is not produced by the implementation of DF–DBIM. A fixed sum N(iter) of Nf₁ and Nf₂ was given, the investigation of simulation results shows that the best value of Nf₁ is [N(iter)/2 − 1]. The error, when applying this way of choosing the parameters, will be normalized with the reduction of 56.11%, compared to use single frequency as used in the conventional DBIM method. The target density along with sound contrast is used to image targets in this paper. It is a fact that low-frequency offers fine convergence, and high-frequency offers fine spatial resolution. Wherefore, this technique can effectively expand DBIM's applicability to the problem of biological tissue reconstruction. Thanks to the usage of empirical data, this work will be further developed prior to its application in reality.
Image Processing, Computer-Assisted ; Methods ; Transducers ; Ultrasonics ; Ultrasonography

This article describes Viet Nam Ministry of Health’s (VMoH) activities to prepare for and respond to the threat Zika virus (ZIKV), including the adaptation of existing surveillance systems to encompass ZIKV surveillance.

Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating infl ammation and fi brosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 (10 µmol/L) treatment as experimental models. Addition of NecroX-5 signifi cantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 (TGFβ1) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, signifi cantly increased production of tumor necrosis factor alpha (TNFα), TGFβ1, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of TNFα, TGFβ1, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway.
Animals ; Decorin ; Fibrosis ; Heart* ; Inflammation ; Liver ; Models, Theoretical ; Phosphorylation ; Rats* ; Reperfusion ; Reperfusion Injury ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

Although the antioxidant and cardioprotective effects of NecroX-5 on various in vitro and in vivo models have been demonstrated, the action of this compound on the mitochondrial oxidative phosphorylation system remains unclear. Here we verify the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity during hypoxia-reoxygenation (HR). Necrox-5 treatment (10 microM) and non-treatment were employed on isolated rat hearts during hypoxia/reoxygenation treatment using an ex vivo Langendorff system. Proteomic analysis was performed using liquid chromatography-mass spectrometry (LC-MS) and non-labeling peptide count protein quantification. Real-time PCR, western blot, citrate synthases and mitochondrial complex activity assays were then performed to assess heart function. Treatment with NecroX-5 during hypoxia significantly preserved electron transport chain proteins involved in oxidative phosphorylation and metabolic functions. NecroX-5 also improved mitochondrial complex I, II, and V function. Additionally, markedly higher peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1alpha) expression levels were observed in NecroX-5-treated rat hearts. These novel results provide convincing evidence for the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity and in preserving PGC1alpha during cardiac HR injuries.
Animals ; Anoxia ; Blotting, Western ; Citric Acid ; Electron Transport ; Heart ; Mitochondria ; Oxidative Phosphorylation* ; Peroxisomes ; Rats ; Real-Time Polymerase Chain Reaction ; Spectrum Analysis

20 patiens avascular necrosis of femoral hip had been treated with vascular pedicle iliac crest grafting same side from 11/2002 - 1/2004. Follow up, longest is 52 weeks, the earliest is 12 weeks. Average age was 38,5. Presumed risk factors were excessive use of alcohol (14/20), the use of corticosteroid prolong (3/20), no specific (3/20). 18 good result patients, 2 not good result patients (both in Ficat IV before operation). None infection, inguinal hernia and limit range of motion of hip. One patient had weak quadriceps (the complete recover after 6 weeks). 10 loss sensation lateral thigh (back normal after average 2 weeks). 2 loss sensation in thigh (back normal after average 2 weeks)
Osteonecrosis ; Therapeutics ; transplantation