Lekha Saha

Iron-deficiency anemia remains the most frequent cause of anemia in pregnancy and is usually amenable to treatment with oral or intravenous iron. Nonetheless, a minority of patients exhibit poor therapeutic response despite adequate dosing and compliance, warranting evaluation for uncommon etiologies such as iron-refractory iron-deficiency anemia (IRIDA). IRIDA is a rare inherited disorder with an autosomal recessive pattern, caused by mutations in the TMPRSS6 gene that lead to inappropriate hepcidin activity and disrupted iron regulation. Here, we present the case of a pregnant Indian woman with persistent microcytic hypochromic anemia that failed to improve with oral iron and showed only modest response to parenteral therapy. Biochemical findings revealed reduced serum iron and low transferrin saturation, indicating defective iron handling. Owing to the refractory nature of the condition, genetic testing was performed, which identified compound heterozygous missense mutations in the TMPRSS6 gene, including a novel variant (c.248T>G). Management included intravenous iron supplementation along with close antenatal surveillance, resulting in stabilization of hemoglobin levels and a satisfactory maternal and fetal outcome. This case emphasizes the importance of considering IRIDA in cases of unexplained treatment-resistant iron-deficiency anemia and highlights the role of molecular diagnostics in establishing a definitive diagnosis.

Background and objectives: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder with unclear etiology, influenced by genetic, environmental, and epigenetic factors. This study investigated the role of gene-specific DNA methylation and transcriptional regulation in North Indian women with PCOS stratified by body mass index (BMI). Methods: Thirty women with PCOS (19 obese, 11 non-obese) and 10 healthy controls (age-matched to both PCOS groups; BMI-matched to non-obese PCOS) were recruited. BMI stratification was intentional to assess obesity-specific epigenetic modifications. Clinical, hormonal, and metabolic parameters were assessed. Promoter-methylation and mRNA expression of 17 candidate genes involved in epigenetic regulation, steroidogenesis, insulin signalling, and cell proliferation were analysed using methylation-specific PCR and qRT-PCR. Correlation matrices were constructed to evaluate associations between methylation and clinical traits. Receiver operating characteristic (ROC) based modelling was used to assess the predictive utility of methylation markers. Results: PCOS-obese participants exhibited significantly elevated testosterone, Luteinising Hormone (LH), and cholesterol levels compared to controls. Vitamin D₃ deficiency was observed in both PCOS subgroups. Epigenetic analysis revealed hypermethylation and downregulation of TET1 and INSIG1 , and hypomethylation-linked overexpression of SF1, CYP11A1, and cell cycle regulators. Correlation analyses revealed associative methylation expression signatures linked with key hormonal parameters ( e.g ., testosterone, LH/FSH ratio) and, to a lesser extent, metabolic traits (associative findings but not mechanistic conclusions). Interpretation and conclusions: This integrative study highlights distinct methylation-expression signatures as hypothesis-generating markers that show statistical association with certain clinical traits, particularly in the obese-PCOS subgroup, but require validation in larger cohorts.

BACKGROUND Drug utilization research has an important role in assisting the healthcare administration to know, compute, and refine the prescription whose principal objective is to enable the rational use of drugs. Research in developing nations relating to the cost of treatment is scarce when compared with developed countries. Thus, the drug utilization research studies from developing nations are most needed, and their number has been growing. AIM To evaluate patterns of utilization of antipsychotic drugs and direct medical cost analysis in patients newly diagnosed with schizophrenia. METHODS The present study was observational in type and based on a retrospective cohort to evaluate patterns of utilization of antipsychotic drugs using World Health Organization (WHO) core prescribing indicators and anatomical therapeutic chemical/defined daily dose indicators. We also calculated direct medical costs for a period of 6 months. RESULTS This study has found that atypical antipsychotics are the mainstay of treatment for schizophrenia in every age group and subcategories of schizophrenia. The evaluation based on WHO prescribing indicators showed a low average number of drugs per prescription and low prescribing frequency of antipsychotics from the National List of Essential Medicines 2015 and the WHO Essential Medicines List 2019. The total mean drug cost of our study was 1396 Indian rupees. The total mean cost due to the investigation in our study was 1017.34 Indian rupees. Therefore, the total mean direct medical cost incurred on patients in our study was 4337.28 Indian rupees. CONCLUSION The information from the present study can be used for reviewing and updating treatment policy at the institutional level.

Cancer cell dormancy (CCD) in colorectal cancer (CRC) poses a significant challenge to effective treatment. In CRC, CCD contributes to tumour recurrence, drug resistance, and amplifying the disease's burden. The molecular mechanisms governing CCD and strategies for eliminating dormant cancer cells remain largely unexplored. Therefore, understanding the molecular mechanisms governing dormancy is crucial for improving patient outcomes and developing targeted therapies. This editorial highlights the complex interplay of signalling pathways and factors involved in colorectal CCD, emphasizing the roles of Hippo/YAP, pluripotent transcription factors such as NANOG, HIF-1α signalling, and Notch signalling pathways. Additionally, ERK/p38α/β/MAPK pathways, AKT signalling pathway, and Extracellular Matrix Metalloproteinase Inducer, along with some potential less explored pathways such as STAT/p53 switch and canonical and non-canonical Wnt and SMAD signalling, are also involved in promoting colorectal CCD. Highlighting their clinical significance, these findings may offer the potential for identifying key dormancy regulator pathways, improving treatment strategies, surmounting drug resistance, and advancing personalized medicine approaches. Moreover, insights into dormancy mechanisms could lead to the development of predictive biomarkers for identifying patients at risk of recurrence and the tailoring of targeted therapies based on individual dormancy profiles. It is essential to conduct further research into these pathways and their modulation to fully comprehend CRC dormancy mechanisms and enhance patient outcomes.

Temporal Lobe Epilepsy (TLE) is a severe neurological condition characterized by recurrent seizures that often do not respond well to available anti-seizure medications. TLE has been associated with epileptogenesis, a process that starts during the latent period following a neurologic insult and is followed by chronic phase. Recent research has linked canonical Wnt signaling to the pathophysiology of epileptogenesis and TLE. Our previous study demonstrated differential regulation of canonical Wnt signaling during early and late stage post status epilepticus (SE) induction. Building on these findings, our current study utilized Wnt modulators: GSK-3β inhibitor 6-bromoindirubin-3’-oxime (6-Bio) and disheveled inhibitor niclosamide and investigated their impact on canonical Wnt signaling during the early (30 days) and later stages (60 days) following SE induction. We assessed several parameters, including seizure frequency, astrogliosis, synaptic density, and neuronal counts in hippocampal tissue. We used immunohistochemistry and Nissl staining to evaluate gliosis, synaptic density, and neuronal counts in micro-dissected hippocampi. Western blotting was used to examine the expression of proteins involved in canonical Wnt/β-catenin signaling, and real-time PCR was conducted to analyze their relative mRNA expression. Wnt modulators, 6-Bio and Niclosamide were found to reduce seizure frequency and various other parameters including behavioral parameters, hippocampal morphology, astrogliosis and synaptic density at different stages of TLE. Graphical Abstract