Voltage-gated sodium channels (VGSCs) play pivotal roles in cancer progression and have emerged as promising therapeutic targets and biomarkers. VGSCs comprise multiple subtypes with distinct tissue distributions, influencing tumour characteristics in different ways. Among these, the tetrodotoxin-sensitive α-subunits and the β1 subunit, commonly found in breast cancer, have been implicated in metastasis and tumour aggressiveness. The NaV1.5 channel and its neonatal variant (nNaV1.5) are overexpressed in aggressive cancers such as breast, prostate, colorectal, and lung cancers, thereby enhancing their invasive capacity. nNaV1.5 is particularly significant due to its tumour-specific expression and strong association with poor prognosis, especially in breast cancer, where it regulates cell proliferation, invasion, and tumour microenvironment remodelling. This review highlights nNaV1.5 as a critical ion channel that drives metastasis through ion regulation, extracellular acidification, and cytoskeletal remodelling. We further evaluate current therapeutic strategies, including siRNA, monoclonal antibodies, and small-molecule inhibitors, while addressing translational challenges such as tumour heterogeneity, drug delivery limitations, and off-target cardiotoxicity due to its similarity with the adult isoform. In addition, we explore the potential of nNaV1.5 as a biomarker subject to epigenetic regulations by factors including RE1-silencing transcription factor (REST) and histone deacetylase 2 (HDAC2), which may facilitate patient stratification and treatment optimization. By integrating mechanistic insights, therapeutic opportunities, and translational challenges, this review goes beyond descriptive summaries to provide a framework for advancing nNaV1.5 research from preclinical studies toward clinical application in cancer therapy.

Plasma biomarkers levels, essential for diagnosing cardiovascular diseases, may vary by ethnicity. In this international prospective study, we compared plasma biomarker levels between European and Asian patients with clinically similar acute heart failure (AHF). Data were collected on emergency admission for acute dyspnea. Blood samples were obtainedwithin 4 hrs of presentation and analyzed for N-terminal pro-B-type natriuretic peptide (NTproBNP), high-sensitivity troponin-T, growth differentiation factor 15, interleukin-6, and C-reactive protein levels. Overall, 907 AHF patients were enrolled; of which, 135 (15%) wereJapanese, and 772 (85%) were European. NT-proBNP levels were significantly higher inHôpital Lariboisière, Bat Viggo Petersen, Porte 5 au 2ème étage, 43 boulevard de la chapelle, Paris 75010, FranceJapanese than in Europeans [4,060 ng/L (interquartile range (IQR) 2,081–12,218) vs.3,390 ng/L (IQR 1,410–7,682), P = 0.004]. After propensity score matching (PSM), no bio-marker levels differed significantly. After stratification according to left ventricular ejection fraction (LVEF) at admission, higher NT-proBNP levels were observed in Japanese AHF pa-tients with LVEF > 50% (P = 0.02) than in European patients. After PSM, the difference was insignificant (P = 0.35). In Asian and Caucasian AHF patients with similar clinical profiles, plasma cardiovascular biomarker levels did not differ significantly, regardless of LVEF, sug-gesting that NT-proBNP and related biomarkers can be applied across these ethnicities.

Purpose: Adjuvant radiotherapy (RT), while effective in reducing cancer recurrence and improving survival rates, often comes with radiation toxicity that can adversely affect the patient’s quality of life (QoL). Evaluating toxicity after RT is crucial because it helps to identify and manage adverse effects that can significantly impact a patient’s QoL. By monitoring toxicity, we can adjust treatment plans to mitigate these effects, improve patient comfort, and ensure a better overall outcome. Therefore this study aimed to evaluate and compare QoL following 3D-conformal hypofractionated RT in breast cancer patients. Methods: We included twenty-one Malaysian women with unilateral breast cancer treated with lumpectomy (n=15) or mastectomy (n=6) followed by 3D-conformal hypofractionated RT. QoL was evaluated using the EORTC QLQ-BR45 questionnaire before, during, and after RT. Results: During RT, there was a significant increase in the mean score of the breast symptoms scale compared to baseline (p=0.002), with the most common symptoms being skin problems, followed by swelling and oversensitivity. However, these symptoms were generally mild for most patients. The other quality of life scales remained stable during RT. Post-RT, most QoL scales showed improvements compared to both baseline and during RT, with significant enhancements in the mean breast symptoms score and breast satisfaction score (all p<0.05). Conclusion: Radiotherapy negatively impacted the QoL of our breast cancer patients, specifically on the breast symptoms scale. However, these symptoms improved after 4 months, resulting in high breast satisfaction and indicating a near-excellent cosmetic outcome. Future studies with larger cohorts are essential to validate these findings, as the small sample size (n=21 at baseline; n=13 post-RT) may have limited the detection of more subtle changes

Parenting children with autism spectrum disorder comes with challenges that impact parenting stress and quality of life, with social support being an influencing factor. The cultural context appears to influence associations between parenting stress, social support, and quality of life. There is a lack of reviews examining these associations in Asia. Thus, this review aims to provide an overview of the relationship between parenting stress, QOL and social support specific to the population in Asian countries. Systematic searches based on PRISMA guidelines were conducted on Medline, Web of Science, and Scopus, which found 26 eligible studies to be included in the review. Findings from the studies demonstrated social support, parenting stress, and quality of life to be significantly associated with each other directly and indirectly. They are also related to multiple variables like coping strategies and self-efficacy. In the future, data from a wider scope of Asian countries will be beneficial since most literature originated from China. Furthermore, more studies on potential moderator and mediator variables could be conducted.

Public interest in cognitive enhancement has driven the widespread availability of dietary supplements claiming to support brain health and memory. This comparative cross-sectional study explores the commercial availability and marketing claims of cognitive-enhancing dietary supplements across offline and online retail platforms. A dual-component design was employed in a comparative cross-sectional study. The first component involved assessing the commercial availability and marketing claims of cognitive-enhancing dietary supplements sold through offline retail outlets in Kuala Lumpur using a purposive sampling approach. The second component consisted of a parallel assessment conducted on online platforms, employing a convenience sampling strategy. A total of 13 products were identified on offline retail platforms in Kuala Lumpur, and 117 products were identified on online platforms. Capsules were the most common dosage form, both offline (46.2%) and online (79.5%). Products sold offline most frequently originated from Singapore (69.2%), whereas online products predominantly came from the United States of America (74.4%). The median prices of offline products were RM 190 (55.5), and online products were RM 196 (183), which are comparable, although the online products exhibited a wider price range (RM14–RM1,147). The most frequent claims were “brain health” for offline products and “memory” for online products. Natural or compound extracts were the most common active ingredients. This study’s findings found significant differences between offline and online dietary supplements in terms of availability, country of origin, price and marketing claims. These inconsistent findings underscore the need for stronger regulation and improved transparency in labelling to safeguard consumer health and ensure product credibility. Future research should focus on dosage accuracy, long-term safety, and mechanisms of action for supplements with cognitiveenhancing claims.

Dialisis merupakan rawatan yang lazim bagi pesakit kegagalan buah pinggang. Dari tahun ke tahun, bilangan pesakit yang menjalani dialisis semakin meningkat dengan kadar yang membimbangkan. Tahap keupayaan fungsi pesakit dialisis adalah lebih rendah berbanding pesakit diabetes yang tidak menjalani dialisis. Kajian ini bertujuan untuk mengenal pasti bagaimana dialisis mempengaruhi prestasi Aktiviti Kehidupan Seharian (ADL) dalam kalangan pesakit diabetes di Kuala Selangor serta faktor-faktor yang mempengaruhi prestasi ADL mereka. Kajian berkaitan prestasi ADL dalam kalangan pesakit dialisis yang menghidap diabetes masih terhad. Oleh itu, kajian ini menggunakan kaedah kualitatif melalui sesi temu bual bersemuka secara separa berstruktur. Seramai sepuluh peserta telah direkrut berdasarkan kriteria kemasukan yang ditetapkan. Lima tema utama telah dikenal pasti daripada temu bual, iaitu: (i) meningkatkan kualiti kehidupan seharian: perspektif baharu terhadap aktiviti harian; (ii) kesan diabetes terhadap aktiviti kehidupan seharian; (iii) kesan dialisis terhadap aktiviti kehidupan seharian; (iv) prestasi fungsi dalam aktiviti asas kehidupan seharian; dan (v) aktiviti harian yang dianggap penting. Hasil kajian menunjukkan bahawa pelbagai jenis aktiviti kehidupan seharian telah terjejas akibat kelemahan fizikal yang dialami oleh peserta. Kajian ini dapat memberi pemahaman yang lebih mendalam kepada ahli terapi cara kerja dan bidang pemulihan lain mengenai keupayaan fizikal pesakit diabetes yang menjalani hemodialisis

BACKGROUND

Penetrating brain injury (PBI) is a leading cause of combat mortality but local outcome data is limited. The authors examined combat-related PBI cases to describe patient characteristics and identify clinical and radiologic predictors of functional recovery

This is a retrospective cohort study of military personnel aged 18–56 years with combat-related PBI referred to VLGH AFPMC between January 2017 to June 2022. The authors collected demographics data, injury mechanism, pre-hospital and transfer details, admission clinical and radiologic findings, treatments, and follow-up outcomes. The Glasgow Outcome Scale (GOS), dichotomized into unfavorable (GOS 1–3) and favorable (GOS 4–5), was used to assess functional status. Associations were tested with Fisher’s Exact Test.

Thirty-seven patients met inclusion criteria: 31 survivors with follow-up and 6 who died in hospital. All were male; gunshot wounds accounted for 81% of injuries. At a median follow-up of 27 months, among survivors, 74% had a Glasgow Coma Scale (GCS) of 15 and 45% achieved good recovery (GOS 5). Pre-hospital timing measures (evacuation time, interval to surgery, and transfer delays) were not significantly associated with outcome. Favorable outcomes correlated strongly with higher admission GCS (p < 0.001), preserved baseline motor function (p < 0.001), smaller hemorrhage volume (p = 0.01), and injury limited to a single lobe (p < 0.001). Unfavorable outcomes were associated with intracranial infection, post-traumatic seizures, and need for multiple surgeries (all p < 0.001).

Functional recovery after combat-related PBI in this cohort was principally determined by initial neurologic status, injury extent, and subsequent complications The lack of association with pre-hospital timing possibly reflects survivorship bias and incomplete capture of early fatalities.

Introduction: Insulin therapy is essential in the management of type 2 diabetes mellitus (T2DM), but is often associated with treatment burden, hypoglycemia, and potential overtreatment. Insulin deintensification is increasingly recommended for appropriately selected patients; however, there is limited real-world evidence to guide patient selection and to identify modifiable factors that influence successful insulin deintensification. This study aimed to identify clinical predictors, including modifiable factors, associated with successful insulin deintensification in a primary care setting. Methodology: A multicentre retrospective observational study was conducted across seven government primary care clinics in the Petaling District. Adult patients with T2DM undergoing insulin deintensification were included. Successful insulin deintensification was defined as maintenance or improvement of hemoglobin A1c following insulin discontinuation, dose reduction, or reduction in injection frequency. Paired outcomes were analyzed using the Wilcoxon signed-rank test. Between-group comparisons were performed using the Mann–Whitney U test and Chi-square or Fisher’s exact test. Multivariable logistic regression was used to identify independent predictors of successful insulin deintensification. Results: A total of 261 patients were included. Glycemic control remained stable following insulin deintensification (p = 0.334). Significant reductions in body weight (−0.41 kg, p = 0.012) and total daily insulin dose (23.1% reduction, p <0.001) were observed. Univariate analysis did not demonstrate significant differences between groups. However, multivariable logistic regression identified SGLT-2 inhibitor use (aOR 3.23, 95% CI 1.28–8.18, p = 0.013) and regular SMBG (aOR 2.00, 95% CI 1.05–3.81, p = 0.035) as independent predictors of successful insulin deintensification. Conclusion Insulin deintensification can be successfully implemented without compromising glycemic control. Identified predictors, including modifiable factors such as SGLT-2 inhibitor use and SMBG, provide clinically actionable insights to guide patient selection and treatment optimization. These findings challenge the traditional reluctance toward insulin deintensification and support a more evidence-based and individualized approach in routine clinical practice.
Primary Health Care ; Insulins

Introduction: Primary aldosteronism (PA), most commonly caused by aldosterone-producing adenomas (APAs), represents the leading form of surgically curable secondary hypertension. While genomic studies have elucidated the mutational landscape of APAs, the spatial organisation and functional role of immune populations across APAs, aldosterone-producing micronodules (APMs), and adjacent adrenal cortex remain poorly defined at single-cell resolution. Methodology: Single-cell RNA sequencing (scRNA-seq) was integrated with spatial transcriptomics in APAs and paired adjacent adrenal cortex, complemented by immunohistochemical (IHC) validation. Immune populations were spatially mapped using canonical markers (CD14, CD68, CD163, HLA-DR, CD8A, and CD4) across defined adrenocortical regions. Results: The adrenal microenvironment in PA demonstrates structured immune organisation rather than passive infiltration. CD14+ monocyte-lineage cells localize intraparenchymally within APAs (n = 10), intercalating between CYP11B2+ aldosterone-producing cells and forming a pattern distinct from perivascular immune niches. scRNA-seq further identified a transcriptionally distinct CD14+ population within the zona reticularis (zR) that co-expresses steroidogenic markers (CYB5A, SULT2A1, TSPAN12) while lacking canonical monocyte transcripts. IHC supported this observation, demonstrating CD14 expression within adrenocortical zR parenchymal cells (n = 5). In parallel, CD4 and HLA-DRA exhibited diffuse cytoplasmic staining within zR parenchymal cells in the absence of classical macrophage marker coexpression (CD68), suggesting non-canonical or context-dependent expression within steroidogenic compartments. CD68+ and CD163+ macrophages were sparsely distributed across APA, APM and adjacent cortex, consistent with lowdensity tissue-resident populations, while CD8A+ cytotoxic lymphocytes were enriched in APAs and APMs with diffuse parenchymal cytoplasmic staining of CD8A additionally observed within the zR. Conclusion These findings reveal a previously unrecognized spatially organised immune-steroidogenic interface within the adrenal cortex. The presence of immune-associated transcriptional and protein signatures within zR cells suggests potential functional plasticity of steroidogenic cells, possibly extending to antigen presentation-related pathways, warranting further mechanistic investigation
Hyperaldosteronism ; Humans