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Fulltext Pulmonary non-tuberculous mycobacterial infections: current state and future management

Chin KL, Sarmiento ME, Alvarez-Cabrera N, Norazmi MN, Acosta A

Eur J Clin Microbiol Infect Dis, 2020 May;39(5):799-826.
PMID: 31853742 DOI: 10.1007/s10096-019-03771-0

Currently, there is a trend of increasing incidence in pulmonary non-tuberculous mycobacterial infections (PNTM) together with a decrease in tuberculosis (TB) incidence, particularly in developed countries. The prevalence of PNTM in underdeveloped and developing countries remains unclear as there is still a lack of detection methods that could clearly diagnose PNTM applicable in these low-resource settings. Since non-tuberculous mycobacteria (NTM) are environmental pathogens, the vicinity favouring host-pathogen interactions is known as important predisposing factor for PNTM. The ongoing changes in world population, as well as socio-political and economic factors, are linked to the rise in the incidence of PNTM. Development is an important factor for the improvement of population well-being, but it has also been linked, in general, to detrimental environmental consequences, including the rise of emergent (usually neglected) infectious diseases, such as PNTM. The rise of neglected PNTM infections requires the expansion of the current efforts on the development of diagnostics, therapies and vaccines for mycobacterial diseases, which at present, are mainly focused on TB. This review discuss the current situation of PNTM and its predisposing factors, as well as the efforts and challenges for their control.
Fulltext MicroRNA-668-3p Mediates Macrophage M2 Polarization by Targeting NFKBIA to Affect Gastric Cancer Cell Proliferation and Migration

Chu C, Liu B, Zhang Y, Xu Z, Wang B, Chin KL

Tohoku J Exp Med, 2024 Nov 07.
PMID: 39505541 DOI: 10.1620/tjem.2024.J115
Impacts of MDR/XDR-TB on the global tuberculosis epidemic: Challenges and opportunities

Chin KL, Anibarro L, Chang ZY, Palasuberniam P, Mustapha ZA, Sarmiento ME, et al.

Curr Res Microb Sci, 2024;7:100295.
PMID: 39512261 DOI: 10.1016/j.crmicr.2024.100295

Tuberculosis (TB) is the world's second-deadliest infectious disease. Despite the availability of drugs to cure TB, control of TB is hampered by the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). The presence of MDR/XDR-TB is alarming due to the low detection rate, high treatment failure, and high mortality. The increasing cases of MDR/XDR-TB are mainly due to the limitations in the diagnostic tests to detect the drug susceptibility of the pathogen, which contribute to the spread of the disease through close contacts. Moreover, inconsistent drug therapy or unsuitable drug regimens could also lead to the subsequent development of drug resistance. The close contacts of an index MDR/XDR-TB patient are at increased risk of developing MDR/XDR-TB. Also, the BCG vaccine may exhibit varying protective effects due to BCG strain diversification, host immune status, exposure to environmental non-tuberculous mycobacteria (NTM), and differences in Mycobacterium tuberculosis (Mtb) subspecies infection, as in the case of sub-optimal protection in the case of Beijing family genotypes of Mtb. This review provides an overview of the current state of drug-resistant tuberculosis (DR-TB) within the context of the global TB pandemic, with a focus on diagnosis, treatment, and the potential impact of BCG vaccination. It highlights the limitations of current approaches and aims to identify opportunities for improving TB control strategies.
Fulltext Identification of Five Novel Salmonella Typhi-Specific Genes as Markers for Diagnosis of Typhoid Fever Using Single-Gene Target PCR Assays

Goay YX, Chin KL, Tan CL, Yeoh CY, Ja'afar JN, Zaidah AR, et al.

Biomed Res Int, 2016;2016:8905675.
PMID: 27975062

Salmonella Typhi (S. Typhi) causes typhoid fever which is a disease characterised by high mortality and morbidity worldwide. In order to curtail the transmission of this highly infectious disease, identification of new markers that can detect the pathogen is needed for development of sensitive and specific diagnostic tests. In this study, genomic comparison of S. Typhi with other enteric pathogens was performed, and 6 S. Typhi genes, that is, STY0201, STY0307, STY0322, STY0326, STY2020, and STY2021, were found to be specific in silico. Six PCR assays each targeting a unique gene were developed to test the specificity of these genes in vitro. The diagnostic sensitivities and specificities of each assay were determined using 39 S. Typhi, 62 non-Typhi Salmonella, and 10 non-Salmonella clinical isolates. The results showed that 5 of these genes, that is, STY0307, STY0322, STY0326, STY2020, and STY2021, demonstrated 100% sensitivity (39/39) and 100% specificity (0/72). The detection limit of the 5 PCR assays was 32 pg for STY0322, 6.4 pg for STY0326, STY2020, and STY2021, and 1.28 pg for STY0307. In conclusion, 5 PCR assays using STY0307, STY0322, STY0326, STY2020, and STY2021 were developed and found to be highly specific at single-gene target resolution for diagnosis of typhoid fever.
Small RNA datasets of drug-susceptible Mycobacterium tuberculosis strains from Sabah, Malaysia

Jumat MI, Jani J, Mustapha ZA, Rodrigues KF, Azizan N, Acosta A, et al.

Data Brief, 2023 Feb;46:108795.
PMID: 36483477 DOI: 10.1016/j.dib.2022.108795

These datasets present a list of small RNAs from three drug-susceptible Mycobacterium tuberculosis strains isolated from Sabah, Malaysia. Sputum samples were obtained from three tuberculosis patients belonging to different districts. The bacteria were detected using GeneXpert MTB/RIF, isolated and cultured in BACTECTM MGITTM 320, and tested for their drug susceptibility. Total RNAs were extracted, sequenced, and analyzed using bioinformatic tools to filter out small RNA present in the Mycobacterium tuberculosis strains. Small RNA sequencing generated total raw reads of 63,252,209, 63,636,812, and 61,148,224 and total trimmed reads (15-30 nucleotides) of 51,533,188, 53,520,197, and 51,363,772 for Mycobacterium tuberculosis strain SBH49, SBH149, and SBH372, respectively. The raw data were submitted to the Sequence Read Archive (SRA) database of the National Center for Biotechnology Information (NCBI) under the accession numbers of SRX16744291 (SBH49), SRX16744292 (SBH149), and SRX16744293 (SBH372). Small RNAs play important roles in cellular processes such as cell differentiation, cell signaling, development of resistance to antibiotics and immune response, and metabolism regulation. The small RNAs determined here could provide further insights into various cellular processes crucial for Mycobacterium tuberculosis survivability and a better understanding of their gene regulation which ultimately opens a new pathway for combating tuberculosis infection.
Fulltext Case report: Ultrasound-guided median nerve electrical stimulation on functional recovery of hemiplegic upper limb after stroke

Li R, Zhang P, Lu J, Zhuang J, Wang M, Fang H, et al.

Front Neurol, 2023;14:1244192.
PMID: 38046582 DOI: 10.3389/fneur.2023.1244192

BACKGROUND: Functional restoration of hemiplegic upper limbs is a difficult area in the field of neurological rehabilitation. Electrical stimulation is one of the treatments that has shown promising advancements and functional improvements. Most of the electrical stimulations used in clinical practice are surface stimulations. In this case, we aimed to investigate the feasibility of a minimally invasive, ultrasound-guided median nerve electrical stimulation (UG-MNES) in improving the upper limb motor function and activity of a patient with right-sided hemiparesis.
CASE PRESENTATION: A 65-year-old male recovering from a left massive intracerebral hemorrhage after open debridement hematoma removal had impaired right limb movement, right hemianesthesia, motor aphasia, dysphagia, and complete dependence on his daily living ability. After receiving 3 months of conventional rehabilitation therapy, his cognitive, speech, and swallowing significantly improved but the Brunnstrom Motor Staging (BMS) of his right upper limb and hand was at stage I-I. UG-MNES was applied on the right upper limb for four sessions, once per week, together with conventional rehabilitation. Immediate improvement in the upper limb function was observed after the first treatment. To determine the effect of UG-MNES on long-term functional recovery, assessments were conducted a week after the second and fourth intervention sessions, and motor function recovery was observed after 4-week of rehabilitation. After completing the full rehabilitation course, his BMS was at stage V-IV, the completion time of Jebsen Hand Function Test (JHFT) was shortened, and the scores of Fugl-Meyer Assessment for upper extremity (FMA-UE) and Modified Barthel Index (MBI) were increased. Overall, the motor function of the hemiplegic upper limb had significantly improved, and the right hand was the utility hand. Electromyography (EMG) and nerve conduction velocity (NCV) tests were normal before and after treatment.
CONCLUSION: The minimally invasive, UG-MNES could be a new alternative treatment in stroke rehabilitation for functional recovery of the upper limbs.
Fulltext First whole genome sequencing data of a Mycobacterium tuberculosis STB-T1A strain isolated from a spinal tuberculosis patient in Sabah, Malaysia

Chin KL, Suing EJ, Andong R, Foo CH, Chan SK, Jani J, et al.

Data Brief, 2024 Jun;54:110476.
PMID: 38725551 DOI: 10.1016/j.dib.2024.110476

Spinal tuberculosis, also referred to as Pott's disease, presents a significant risk of severe paralysis if not promptly detected and treated, owing to complications such as spinal cord compression and deformity. This article presents the genetic analysis of a Mycobacterium tuberculosis STB-T1A strain, isolated from the spine of a 29-year-old female diagnosed with spinal tuberculosis. Genomic DNA was extracted from pure culture and subjected to sequencing using the Illumina NovaSeq 6000 sequencing system. The genome of the M. tuberculosis STB-T1A strain spans 4,367,616 base pairs with a G+C content of 65.56 % and 4174 protein-coding genes. Comparative genomic analysis, conducted via single nucleotide polymorphism (SNP)-based phylogenetic analysis using the Maximum Likelihood method, revealed that the strain falls within the Indo-Oceanic lineage (Lineage 1). It clusters with the M. tuberculosis 43-16836 strain, which was isolated from the cerebrospinal fluid of a patient with tuberculous meningitis in Thailand. The complete genome sequence has been deposited at the National Center for Biotechnology Information (NCBI) GenBank database with the accession number JBBMVZ000000000.
Engineered Mycobacterium tuberculosis antigen assembly into core-shell nanobeads for diagnosis of tuberculosis

Sheffee NS, Rubio-Reyes P, Mirabal M, Calero R, Carrillo-Calvet H, Chen S, et al.

Nanomedicine, 2021 06;34:102374.
PMID: 33675981 DOI: 10.1016/j.nano.2021.102374

Despite recent advances in diagnosis, tuberculosis (TB) remains one of the ten leading causes of death worldwide. Here, we engineered Mycobacterium tuberculosis (Mtb) proteins (ESAT6, CFP10, and MTB7.7) to self-assemble into core-shell nanobeads for enhanced TB diagnosis. Respective purified Mtb antigen-coated polyester beads were characterized and their functionality in TB diagnosis was tested in whole blood cytokine release assays. Sensitivity and specificity were studied in 11 pulmonary TB patients (PTB) and 26 healthy individuals composed of 14 Tuberculin Skin Test negative (TSTn) and 12 TST positive (TSTp). The production of 6 cytokines was determined (IFNγ, IP10, IL2, TNFα, CCL3, and CCL11). To differentiate PTB from healthy individuals (TSTp + TSTn), the best individual cytokines were IL2 and CCL11 (>80% sensitivity and specificity) and the best combination was IP10 + IL2 (>90% sensitivity and specificity). We describe an innovative approach using full-length antigens attached to biopolyester nanobeads enabling sensitive and specific detection of human TB.