Performance Comparison Between Conventional Fluorescent Spot Test and Quantitative Assay in Detecting G6PD Deficiency in Neonates

Objectives: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy worldwide. The fluorescent spot test (FST) is the conventional method for screening neonates for G6PD. However, it has limitations and quantitative assays such as the CareStart Biosensor 1 are being increasingly recommended. This study aimed to compare FST and CareStart Bioensor 1 in their ability to detect G6PD levels in neonates. Methods: This cross-sectional study involved 455 neonates between June and December 2020. Two milliliters of cord blood were analyzed with CareStart Biosensor 1 and dried cord blood spots with FST. Data was recorded and statistically analyzed. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to determine the performance of FST at specific G6PD cut-off values; Cohen’s kappa analysis assessed the agreement between the two methods. Results: The sensitivity of FST at 30% cut-off G6PD activity level was 91.0%, (95% CI: 57.0–100) and specificity of 97.0% (95% CI: 95.0–98.0). At 60% cut-off, the FST sensitivity sharply declined to 29.0% (95% CI: 19.0–40.0) with a specificity of 100% (95% CI: 98.0–100). The overall prevalence of G6PD deficiency was 5.1% as measured by FST and 17.8% by Biosensor 1 (p< 0.001). Conclusions: In this study, FST missed a significant proportion of cases of intermediate G6PD levels. FST also misclassified several G6PD intermediate individuals as normal, rendering them susceptible to oxidative stress. Biosensor 1 reported a significantly higher prevalence of G6PD deficiency

Dysregulation of Non-Coding RNAs: Roles of miRNAs and lncRNAs in the Pathogenesis of Multiple Myeloma

The dysregulation of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), leads to the development and advancement of multiple myeloma (MM). miRNAs, in particular, are paramount in post-transcriptional gene regulation, promoting mRNA degradation and translational inhibition. As a result, miRNAs can serve as oncogenes or tumor suppressors depending on the target genes. In MM, miRNA disruption could result in abnormal gene expression responsible for cell growth, apoptosis, and other biological processes pertinent to cancer development. The dysregulated miRNAs inhibit the activity of tumor suppressor genes, contributing to disease progression. Nonetheless, several miRNAs are downregulated in MM and have been identified as gene regulators implicated in extracellular matrix remodeling and cell adhesion. miRNA depletion potentially facilitates the tumor advancement and resistance of therapeutic drugs. Additionally, lncRNAs are key regulators of numerous cellular processes, such as gene expression, chromatin remodeling, protein trafficking, and recently linked MM development. The lncRNAs are uniquely expressed and influence gene expression that supports MM growth, in addition to facilitating cellular proliferation and viability via multiple molecular pathways. miRNA and lncRNA alterations potentially result in anomalous gene expression and interfere with the regular functioning of MM. Thus, this review aims to highlight the dysregulation of these ncRNAs, which engender novel therapeutic modalities for the treatment of MM.</p

Blood transfusion knowledge among nurses in Malaysia:a university hospital experience

Blood transfusion is a fundamental and life-saving procedure where the consequence of errors can be fatal. Nurses’ knowledge plays an essential role in ensuring quality and safety in blood transfusion. The objective of this study was to assess blood transfusion-associated knowledge of tertiary hospital nurses on the east coast of Malaysia. This was a cross-sectional study with 200 registered nurses involved in blood transfusion procedures at Hospital Universiti Sains Malaysia. The knowledge of the nurses was evaluated by using the routine blood transfusion knowledge questionnaire based on five parts, and <50%, 50–74%, or ≥75% of the knowledge was considered as poor, moderate, or high, respectively. Based on the scoring system, the overall knowledge of blood transfusion among Malaysian nurses (33.2 ± 8.4 years) was estimated to be 54.9 ± 7.6%. In individual items, the scoring was 81.0%, 45.4%, 49.2%, 63.0%, and 90.0% in knowledge prior to blood transfusion, on pre-transfusion, on post-transfusion, on complications, and on transfusion policy, respectively. The findings of this study indicated that most of the nurses’ overall knowledge of blood transfusion was at a moderate level; therefore, training courses and continuous medical education are warranted to improve knowledge and skills of the nurses to ensure good practices of blood transfusion

The first Malay database toward the ethnic-specific target molecular variation

BACKGROUND:The Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9(th) October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb). FINDINGS:Currently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP ( http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register ). CONCLUSIONS:This database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background

Apoptotic induction in CCRF-CEM and HL-60 human leukemic cell lines by 5-Azacitidine and trichostatin A.

The aims of the study were to investigate the anti-cancer effects of 5Aza and TSA in two leukemic cell lines (CCRF-CEM and HL-60). Inhibition concentration of 5-Aza and TSA were measured using trypan blue exclusion assay. 5-Aza and TSA at IC50 were treated to both CCRF-CEM and HL-60 cell lines for 4-6 days. To confirm the inhibition effects of these agents, Annexin-V stained cells were analyzed using flow cytometry to evaluate the apoptotic induction. The IC50 values of CCRF-CEM were 2.01±0.1µM and 2.65±0.3µM for 5-Aza- and TSA-treated, respectively. Whereas, the IC50 values of HL-60 were 1.98±0.2µM and 2.35±0.2µM for 5-Aza- and TSA-treated, respectively. To further substantiate the findings, the time-dependent exposure of both drugs was studied. CCRF-CEM cells were reduced to 49.4%±5.0, 49.4%±2.5 and 41.5%±5.6 by 5-Aza; 56.5%±7.0, 45.3%±4.2 and 40.2%±4.2 by TSA treatment at first, third and sixth day. HL-60 cells were reduced to 72.0%±4.5, 51.0%±1.5 and 40.6%±2.6 by 5-Aza at first, third and sixth day. Meanwhile, HL-60 cells reduced to 55.6%±4.5, 45.2%±4.0 and 36.3%±2.9 by TSA at first, second and fourth day. Both cell lines were significantly inhibited (p<0.05) compared to the untreated. Furthermore, flow cytometry demonstrated that 5-Aza and TSA significantly increased the cells population positive for Annexin-V in CCRF-CEM and HL-60 cell lines. In CCRF-CEM, the total apoptotic rates were 51.7%±9.7 and 49.4%±6.0 for 5-Aza- and TSA-treated, while, in HL-60, the apoptotic rates were 51.0%±3.9 and 49.7%±9.6 for 5-Aza- and TSA-treated, in a dose- and time-dependent manner, respectively. Epigenetic modification drugs, 5-Aza and TSA have anti-leukemic effects and induce apoptosis at micro-molar concentrations in CCRF-CEM and HL-60 leukemic cell lines. These results may provide a new insight into the use of 5-Aza and TSA in inhibiting the growth of leukemic cells and useful strategy in developing an epigenetic therapy

Forensic short tandem repeat markers alteration in cancerous tissues: a scoping review

Abstract Background Short Tandem Repeats (STRs) are segments of DNA composed of a short sequence of nucleotides that repeat consecutively. These repeating sequences exhibit distinct lengths and nucleotide sequences among individuals, showcasing high variability and uniqueness. The STR profile remains consistent across all cells in an individual’s body. Nonetheless, changes in the STR profile have been documented in cancerous tissues. This scoping review aimed to investigate the occurrence and pattern of forensic STR markers alterations in cancerous tissues. We conducted a scoping review of the English-language publications published between 2002 and 2022 in the PubMed, Science Direct, and Scopus databases and a manual search of reference lists from reviewed papers. The review was carried out in compliance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. Results Our search resulted in a total of 1,065 articles associating forensic STR studies with cancerous tissues. A total of 18 of these studies met our inclusion criteria. The D18S51 marker was most often found to be altered when associated with cancers such as breast, colorectal, gastric, gynaecology, and lung cancers. Following with that, FGA, VWA, D19S433, and D13S317 markers could as well be seen to have allelic alteration in cancerous tissues. Four other STR markers (TPOX, D7S820, D2S1338, and Penta D) could be potentially represented as stable STR markers in cancerous tissues. Conclusions According to our review, colorectal cancer tissue has the highest level of genomic instability compared to that of other cancer types. In summary, the genetic instability caused by faulty DNA mismatch repair processes in human carcinomas can pose challenges for forensic genotyping and DNA profile matching

The Role of Epigenetics in the Development and Progression of Multiple Myeloma

Multiple myeloma (MM) is an exceptionally complicated and heterogeneous disease that is caused by the abnormal proliferation of malignant monoclonal plasma cells initiated in the bone marrow. In disease progression, a multistep process including differentiation, proliferation, and invasion is involved. Despite great improvement in treatment outcomes in recent years due to the substantial discovery of novel therapeutic drugs, MM is still regarded as an incurable disease. Patients with MM are afflicted by confronting remission periods accompanied by relapse or progression outcomes, which inevitably progress to the refractory stage. In this regard, MM may need new medications or modifications in therapeutic strategies to overcome resistance. A variety of genetic abnormalities (e.g., point mutations, translocations, and deletions) and epigenetic changes (e.g., DNA methylation, histone modification, and non-coding RNA) contribute to the pathogenesis and development of MM. Here, we review the significant roles of epigenetic mechanisms in the development and progression of MM. We also highlight epigenetic pathways as potential novel treatment avenues for MM, including their interplay, use of epigenetic inhibitors, and major involvement in immuno-oncology