Objective. TB recurrence is the second episode of TB after initial treatment bringing about an additional 7% load in TB burden intensified by 17.7% of multidrug-resistant recurrent cases. It is necessary to curb recurrence so that attempts to deal with active disease can be made more effective. This study aimed to characterize sociodemographic and clinical factors associated with recurrent TB in a high-burden setting. Methodology. A retrospective case-control study was carried out at two hospitals in Rawalpindi, Pakistan. TB patients and controls were included in the study. Sociodemographic and clinical data were collected by questionnaire from all subjects. Multivariate regression analysis was performed to determine factors associated with TB and TB recurrence respectively. Results. In our study cohort, factors significantly associated with TB were low BMI (OR: 0.961 (CI 0.954–0.968), ), female gender (OR: 2.065 (CI 1.922–2.219), ), being single/unmarried (OR: 1.214 (CI 1.109–1.328), ), middle-income status (OR: 1.935 (CI 1.616–2.323), ), smoking (OR: 1.567 (CI 1.435–1.710), ), and diabetes mellitus (OR: 1.142 (CI 1.017–1.278), ). TB recurrence constituted 11.2% of patients presenting to the hospital. Compared with the first episode of TB, cases with recurrence were more likely to be older (OR: 1.011 (CI 1.004–1.017), ), have disease awareness (OR: 1.906 (CI 1.486–2.437), ), smear positive (OR: 2.384 (CI 1.650–3.536), ), and be drug-resistant (OR: 5.615 (CI 4.265–7.386), ). Conclusion. In the present study cohort, low BMI, female gender, being single, middle-income status, being unemployed, smoking, and being diabetic came out to be the sociodemographic and clinical risk factors for TB. Further exploring the TB cases increasing age, drug resistance and smear positivity stood out to be the major sociodemographic and clinical factors of TB recurrence despite high disease awareness.

MiR-194-5p/BCLAF1 deregulation in AML tumorigenesis

Autosomal-recessive cerebellar ataxias (ARCAs) are heterogeneous rare disorders mainly affecting the cerebellum and manifest as movement disorders in children and young adults. To date, ARCA causing mutations have been identified in nearly 100 genes; however, they account for less than 50% of all cases. We studied a multiplex, consanguineous Pakistani family presenting with a slowly progressive gait ataxia, body imbalance, and dysarthria. Cerebellar atrophy was identified by magnetic resonance imaging of brain. Using whole exome sequencing, a novel homozygous missense mutation ERCC8:c.176T>C (p.M59T) was identified that co-segregated with the disease. Previous studies have identified homozygous mutations in ERCC8 as causal for Cockayne Syndrome type A (CSA), a UV light-sensitive syndrome, and several ARCAs. ERCC8 plays critical roles in the nucleotide excision repair complex. The p.M59T, a substitution mutation, is located in a highly conserved WD1 beta-transducin repeat motif. In silico modeling showed that the structure of this protein is significantly affected by the p.M59T mutation, likely impairing complex formation and protein-protein interactions. In cultured cells, the p.M59T mutation significantly lowered protein stability compared to wildtype ERCC8 protein. These findings expand the role of ERCC8 mutations in ARCAs and indicate that ERCC8-related mutations should be considered in the differential diagnosis of ARCAs.

Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5–2% population worldwide. The exact etiology is still unknown; however, vitiligo is hypothesized to be a multifactorial and genetically heterogeneous condition. Therefore, the current study is designed to investigate the anthropometric presentation and genetic spectrum of vitiligo in fifteen consanguineous Pakistani families. The clinical evaluation of participating individuals revealed varying degrees of disease severity, with 23 years as the average age of disease onset. The majority of the affected individuals had non-segmental vitiligo (NSV). Whole exome sequencing analysis revealed clustering of rare variants of known vitiligo-associated genes. For instance, in the affected individuals of family VF-12, we identified three novel rare variants of PTPN22 (c.1108C>A), NRROS (c.197C>T) and HERC2 (c.10969G>A) genes. All three variants replaced evolutionarily conserved amino acid residues in encoded proteins, which are predicted to impact the ionic interactions in the secondary structure. Although various in silico algorithms predicted low effect sizes for these variants individually, the clustering of them in affected individuals increases the polygenic burden of risk alleles. To our knowledge, this is the first study that highlights the complex etiology of vitiligo and genetic heterogeneity in multiplex consanguineous Pakistani families.

Introduction: Differentiating TB phenotypes remains a diagnostic challenge due to the absence of a universally accepted standard test. Although the interferon gamma release assay (IGRA) is recommended for Latent TB Infection (LTBI), its application varies across clinical settings. This study utilized IGRA to immunologically categorize subclinical individuals and compare hematological parameters, including the complete blood count (CBC) and differential leukocyte count (DLC) among subclinical, clinical, and cured individuals to assess their diagnostic utility. Methods: IGRA was performed to differentiate TB phenotypes. Demographic data, CBC, and DLC values were recorded. The Mann-Whitney U test was used for intergroup comparisons. Receiver Operating Characteristic (ROC) curve analysis assessed the diagnostic performance of significant markers. Results: IGRA stratified subclinical individuals into LTBI (13.2%) and healthy controls (HC; 86.8%). RBC and TLC were elevated, while platelet counts were reduced in active TB (ATB) compared with HC and LTBI (p 0.83, adjusted OR=1.59). Discussion: The results highlight the potential of hematological markers, particularly NLR and ESR, in distinguishing TB phenotypes. While promising, the findings are limited by smaller sample sizes in the LTBI and TB-CU groups and the absence of IGRA in TB-CU individuals. Conclusion: CBC and DLC parameters vary across TB phenotypes. NLR, neutrophils, ESR, and monocytes show potential as supportive diagnostic tools. Further longitudinal studies are warranted.