Schizophrenia patients demonstrate variations in response to different therapies that are currently being used for the treatment of disorders, such as augmentation therapy (ECT or mood stabilizer) and combination therapy (with antipsychotics). These therapies are also used to treat schizophrenia patients in Pakistan; however, patients show poor overall response. Therefore, this study was conducted to investigate the association between the patients’ response to treatment and the use of antipsychotic agents, with variability in overall response, within different groups of patients. Methods: We conducted a retrospective study that included schizophrenia subjects (N = 200) belonging to different age groups, ethnicities, and regions from different outpatient and inpatient departments in psychiatric institutes located in different cities of Pakistan. These patients were assessed for their response to treatment therapies and categorized into four groups (non-responders (N-R), slow response (S-R), patients with relapse, and completely recovered patients (C-R)) according to their responses. Results: The final analysis included 200 subjects, of which 73.5% were males. Mean age was 34 ± 10 years. Percentage of N-R was 5%, S-R was 42%, patients with relapse were 24%, and C-R was 1.5%. The generalized linear regression model shows a significant association between medication response and age (p = 0.0231), age of onset (p = 0.0086), gender (p = 0.005), and marital status (p = 0.00169). Variability within the medication responses was a result of the treatment regime followed. Antipsychotic agents were significantly associated with the treatment response (p = 0.00258, F = 4.981) of the patients. Significant variation was also observed in the treatment response (p = 0.00128) of the patients that were given augmentation therapy as well as combination therapy. Conclusion: The data suggests proper monitoring of patients’ behavior in response to treatment therapies to implement tailored interventions. Despite several genetic studies supporting the heritability of schizophrenia, an insignificant association between characteristic features and family history might have been due to the limited sample size, suggesting collaborative work with massive sample sizes.
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.
7 September 2023 in Bangladesh Journal of Medical Science
Objective: Tuberculosis (TB) is among the widespread and rapidly growing infections in the world. Furthermore, TB is one of the major public health problems in Pakistan as every year 48,000 Pakistani dies due to this infection. Pakistan ranks fifth among high burden countries worldwide. As the TB has become most threatening because of the epidemics of human immune deficiency virus (HIV), Covid-19 and the emergence of multi-drug resistance (MDR) strains of Mycobacterium tuberculosis (M. tb). This study was aimed to understand the genetic mechanism of drug resistance in local TB isolates. Methodology: For the genetic studies of INH resistance, KatG (encoding catalase peroxidase) hotspot region was amplified through PCR followed by RFLP and sequencing. Results: The study of PCR-RFLP showed that forty-five out eighty INH resistant M. tb strains had mutations in KatG (codon 315) which is 56.2% of all cases. Sequencing results revealed that this is substitution mutation; AGC to ACC (Ser315Thr). Conclusion: It may be concluded that majority of INH resistance is due to the mutation in the codon 315 of KatG in local isolates. Furthermore, PCR-RFLP technique could be considered as a reliable method for the early detection of KatG mutations in MDR-TB. Bangladesh Journal of Medical Science Vol. 22 No. 04 October’23 Page : 804-808
27 July 2023 in Seizure: European Journal of Epilepsy
Objectives: The purpose of the study was to determine the prevalence of biofilm production and resistance to several antibiotics in P. aeruginosa isolated from post-surgical wound infections at a tertiary hospital. It also investigated the relationship between biofilm formation and drug resistance.Methods: The research was a cross-sectional study carried out between November 2024 and October 2025 on 116 non-duplicate P. aeruginosa isolates in patients with clinically diagnosed PSWIs. Standard microbiological techniques were used to identify isolates. The Kirby-Bauer disk diffusion technique was used to test antimicrobial susceptibility according to CLSI 2024 standards. The Tissue Culture Plate (microtiter plate) method was used to quantitatively measure biofilm production. Thestatistical analysis was conducted with SPSS 26.0, and the p-value was considered significant below 0.05.Results: Polymyxins (colistin and polymyxin B) exhibited the highest susceptibility rates (96.6% and 94.8%, respectively), while the lowest susceptibility was observed against ciprofloxacin (44.0%). Overall, 52 (44.8%; 95% CI: 35.9–53.9%) isolates were MDR, and 18 (15.5%; 95% CI: 9.5–23.5%) were XDR. Biofilm production was detected in 93 (80.2%) isolates, with 24 (20.7%) classified as strong producers. Using the Chi-square test for trend, we found a statistically significant relationship between biofilm formation and MDR (p < 0.001), with strong biofilm producers exhibiting markedly higher resistance to multiple antibiotics, including ciprofloxacin (87.5%) and meropenem (62.5%).Conclusion: The study shows high biofilm production and resistance to antimicrobials (MDR and XDR) of P. aeruginosa in post-surgical wound infections (PSWIs). This observation reveals a therapeutic dilemma, which suggests screening for biofilm and judicious use of antibiotics, along with adjunct therapies, such as biofilm-disrupting agents, to treat PSWIs.
Background and Objectives: Pseudomonas aeruginosa (P. aeruginosa), a multidrug-resistant bacterium, represents a con- siderable risk in healthcare environments owing to its capacity to induce various infections. The resistance of P. aeruginosa is frequently linked to efflux pumps that actively remove antibiotics from the bacterial cell. This study investigates novel amide compounds as potential alternatives to address P. aeruginosa isolates exhibiting multidrug resistance mediated by efflux pumps. Materials and Methods: Gram staining and biochemical assays revealed thirty-three multi-drug-resistant P. aeruginosa iso- lates from a tertiary care hospital Peshawar. After antibiotic susceptibility testing, efflux pumps were detected using Ethidium Bromide (EtBr) agar cartwheel technique and UV transilluminator. Novel amides were tested for efflux pump and anti-pseu- domonal action against efflux pump-positive isolates utilizing agar well diffusion and micro broth dilution, including synergy with ciprofloxacin and gentamicin. Results: Three high efflux pump activity P. aeruginosa isolates were chosen using ETBr agar cartwheel technique. Novel amides (ITC, ITD, ITE, DEP) block efflux pump, although TEM-cu is very antimicrobial. TEM-cu, DEP, ITC, and ITE have 0.19, 0.78, and 0.78 mg/ml MICs. Effectiveness against efflux pump-expressing P. aeruginosa is lowest with ITE (1.56 mg/ ml). Together with ciprofloxacin and gentamicin, TEM-cu and DEP improved antimicrobial effectiveness. Conclusion: TEM-cu is highly effective against efflux pump-positive P. aeruginosa, while amides like ITC, ITD, ITE, and DEP block these pumps. With significant reductions, DEP and TEM-cu improve ciprofloxacin and gentamicin efficacy. This method may help overcome P. aeruginosa efflux pump-mediated resistance.