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Introduction Anorectal diseases are prevalent in the general population and may vary from benign disorders to malignant lesions that can metastasize. There is a variety of proctologic symptoms associated with each disease. The incidence of proctologic disease varies in different cultures due to dietary habits and variations in lifestyle. The present study was conducted to determine the spectrum of different proctologic diseases in female patients presenting with proctologic symptoms. Methods This cross-sectional study was conducted in the Surgery Department of Mardan Medical Complex, Mardan, and Khyber Teaching Hospital, Peshawar, from January 2022 to January 2023. Female patients with proctologic symptoms were included, while non-consenting patients were excluded. After obtaining a detailed history and examination by the experienced surgeon, digital rectal examination and proctoscopy/sigmoidoscopy were performed where necessary. Diagnoses were made, and the data regarding proctologic symptoms and their corresponding diagnoses was analyzed using Statistical Package for the Social Sciences (SPSS) version 20.0 (IBM SPSS Statistics, Armonk, NY) using mean and standard deviation for quantitative variables and frequency and percentage for qualitative variables. Results The mean age of 500 female study participants was 38.35±16.305 (range: 7-108) years. Bleeding per rectum, constipation, and pain per rectum were the commonest proctologic symptoms seen in 341 (68.2%), 287 (57.4%), and 272 (54.4%) cases, respectively. Anal fissures and hemorrhoids were the commonest proctologic diseases seen in 264 (52.8%) and 60 (12%) cases, respectively. Conclusion Bleeding per rectum is the commonest proctologic symptom in patients. Anal fissures and hemorrhoids are the commonest proctologic diseases in our setup. Bleeding per rectum and hemorrhoids in the female population cause loss of blood, which in turn will aggravate the clinical picture of underlying anemia, if any.
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Pyrazinamide (PZA) is the first-line drug commonly used in treating Mycobacterium tuberculosis (Mtb) infections and reduces treatment time by 33%. This prodrug is activated and converted to an active form, Pyrazinoic acid (POA), by Pyrazinamidase (PZase) enzyme. Mtb resistance to PZA is the outcome of mutations frequently reported in pncA, rpsA, and panD genes. Among the mentioned genes, pncA mutations contribute to 72-99% of the total resistance to PZA. Thus, considering the vital importance of this gene in PZA resistance, its frequent mutations (D49N, Y64S, W68G, and F94A) were investigated through in-depth computational techniques to put conclusions that might be useful for new scaffolds design or structure optimization to improve the efficacy of the available drugs. Mutants and wild type PZase were used in extensive and long-run molecular dynamics simulations in triplicate to disclose the resistance mechanism induced by the above-mentioned point mutations. Our analysis suggests that these mutations alter the internal dynamics of PZase and hinder the correct orientation of PZA to the enzyme. Consequently, the PZA has a low binding energy score with the mutants compared with the wild type PZase. These mutations were also reported to affect the binding of Fe2+ ion and its coordinated residues. Conformational dynamics also revealed that ß-strand two is flipped, which is significant in Fe2+ binding. MM-GBSA analysis confirmed that these mutations significantly decreased the binding of PZA. In conclusion, these mutations cause conformation alterations and deformities that lead to PZA resistance.
