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Introduction: Toxoplasma gondii (TG), Rubella virus (RV), Cytomegalovirus (CMV), and Herpes simplex virus (HSV) 1 and 2, globally most neonatal and infant deaths are reported due to this group of infections. Purpose: The objective of this research study is to estimate the Prevalence of TORCH infections. Methods: This research study was carried out at the Hi-Tech clinical laboratory Shewa Adda Swabi KPK Pakistan for a duration of 4 months from April 2022 to July 2022. Data statistics looking at the clinical characteristics of Toxoplasma gondii, CMV, RV, and HSV were filled from n=371. All samples were qualitative and quantitative tested by using Immune chromatographic (ICT) and Chemiluminescence Microparticle Immunoassay (CMIA) techniques. Results: Out of n=317 pregnant women, n=131 (35 %) women were found positive while n=240 (65 %) women were found negative. Prevalence of Toxoplasma gondi 32 %, RV 28 %, CMV 27 %, and HSV 13 % in Swabi, KPK, and Pakistan. Among them, a high-frequency fraction of co-infection was detected for CMV and Rubella 17 (58 %), followed by CMV, Herpes, Rubella virus, and Toxoplasma gondii combined 7(25 %). The highest number of infected individuals 37 % we found in the age-group 21-25 years, followed by the 15-20 years age group 23 %, 26-30 years age group 17 %, 31-35 years age group 23 % while the lowest number of positive individuals found in >36 age group. Conclusion: In brief context, TORCH pathogens have potentially shocking clinical manifestations. Hence, screening before pregnancy, and timely diagnosis of TORCH can reduce disease and death in both kid, and the mother. Moreover, knowing the epidemiology survey is a significant aspect to develop strategies and implementation for the prevention of disease. Keywords: Pregnancy, Prevalence, TORCH, Swabi, Infections.

Background: Hepatitis C virus (HCV) is a major cause of morbidity and mortality. About 71 million people around the world are chronically infected with HCV, however, in Pakistan, approximately 12 million people are suffering from this dreadful virus. In Pakistan, approximately 6.2 % of population is infected with HCV and its treatment rate is approximately 1 %. The aim of this research was to assess thyroid hormones level in chronic HCV patients which were taking the oral-antiviral therapy. Methods: A total of 1650 suspects were screened by immunochromatographic technique. Then ELISA technique were used to confirmed the sample and PCR were also performed. All data were analyzed through Microsoft Excel and SPSS-21. Results: Out of total ICT positive, 117 patients were positive for HCV. Subsequently, all positive samples were exposed to Enzyme linked Immunosorbant assay, out of 117 tested samples 112 (6.7 %) were found positive. However, the final confirmation was done by using Real Time PCR, which showed 109 (6.6 %) patients positive for HCV. Among these 109 HCV patients, the age-wise prevalence of HCV patients was observed maximum 35 (32 %) in age group (55-74 years). Furthermore, these 109 patients were tested for the thyroid dysfunction, before and after anti-viral therapy (Sofosbuvir and Daclatasvir therapy) which was recommended by World Health Organization. Out of 109 HCV positive patients the frequency, 92 (84.6 %) showed euthyroidism, 6 (5.5 %) hypothyroidism and 11 (10 %) hyperthyroidism. Thyroid dysfunction was high (n=17, 15.6 %) in patients with age above 50 years. Six (35.2 %) of thyroid dysfunction patients revealed hypothyroidism and hyperthyroidism was observed in 11 (64.7 %) patients. Mean values of thyroid function test before antiviral therapy were TSH = 3.88 ± 1.0, TT3 = 1.15 ± 0.58, and TT4 = 7.7 ± 01.99 and mean values after three months therapy were TSH = 2.49±1.72, TT3 =1.38 ± 0.69 and TT4 = 8.78 ± 2.29. Conclusion: It is concluded that HCV infected individuals on oral antiviral drugs have an effect on the thyroid gland, therefore, HCV patients should be frequently screened for thyroid disorders before and after treatment to ensure euthyroid status. Keywords: Thyroid hormones, Hepatitis, Oral Anti-viral therapy, Thyroidism

Diabetes Mellitus is one of the major worldwide public health issues, along with socio-economic growth. Diabetes Mellitus is a chronic metabolic syndrome of several causes characterized by long-lasting hyperglycemia with the turmoil of carbohydrates. The study aimed to evaluate pharmacotherapy on rational grounds for drug-drug interactions, polypharmacy, and untreated conditions if any., For the recording of patient case histories, a standard questionnaire was designed, which includes age, sex, history, chief complaints, Clinical tests, diagnosis & patient’s family history, etc., the copy of which is appended. Considering 20 cases, different parameters were studied which showed that 17 out of 20 cases received rational therapy according to standard pharmacotherapy and the patients responded well to the prescribed therapy, 3 cases out of 20 received irrational therapy due to which they showed poor response. The percentage of the female patient was 40% and the male patient was 60%. In some of these cases, drug interactions were found and their percentage was 22.1%. The most prominent interaction occurrence was of Ramipril with metformin i.e. 18.75% and Ciprofloxacin interaction with glimepiride is 6.25% etc. In all cases, a total of 86 drugs related problems were reported. The percentage of untreated conditions was 9.3%, drug without indication 6.98%, and cost-related problems were 20.9%, etc. In some cases, concurrent diseases were also found i.e. hypertension at 37.5% and asthma at 25 was prominent. Patients with ages between 41-50 and 51-60 years have a high percentage of Diabetes Mellitus i.e. 40% and 40% respectively. The most prominent ADRs were insomnia, skin rashes, dizziness, nausea, vomiting, diarrhea, etc. Nausea, vomiting, and diarrhea are more frequent with antibiotics. Keywords: Epidemiology, Etiology, Pathophysiology, Investigations, Complications and Treatment of Diabetes Mellitus

Bacterial urinary tract infection (UTI) is one of the utmost prevailing bacterial diseases that affect both sexes at different ages. Due to emerging multi-drug resistant (MDR) bacteria, it is necessary to investigate the antibiotic susceptibility pattern of the bacterial agents to improve the empirical treatment. In this study, we collected a total of 142 urine samples from infected individuals of both sexes at Al-khidmat diagnostics and blood bank from January to March 2022. Different antibiotic susceptibility patterns of the bacterial isolates were examined by using the disk diffusion method. The UTI was reported in 21 (15 %) males and 119 (85 %) females. the highest number of positive individuals are found in middle and old age groups respectively 40 % and 44 %. While 96 % of uropathogens are gram-positive and only 3 % of cases were caused by gram-negative bacteria. The most prevalent pathogen was E.coli 62 % and followed by Staphylococcus Aureus 12 %.In study showed that E.coli is 62 % amoxicillin, Cefuroxime 23, Cefixime 48 %, Norfloxacin 24, Penicillins 37 % , Ciprofloxacin 24 %, Gentamycin 8 %, Ceftriaxone 20 %, and Levofloxacin 4 % resistant. The current study concluded that antibiotic resistance among urinary pathogens was raised, and significant variance in antibiotic susceptibility patterns was identified. UTIs can be treated with medicines such as Levofloxacin, Gentamycin, Teicoplanin, and Moxifloxacin. This study's findings indicate that future research should focus on the causes of resistance to identify solutions to this crucial problem, as well as on the use of health education to prevent drug usage. Keywords: Uropathogens, Antibiotics, Urinary tract infection, UTI, MDR

Hepatitis C virus (HCV) has a positive sense single-stranded enveloped RNA virus. HCV is one of the most common blood-borne diseases causing significant morbidity and mortality globally. HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death. World Health Organization reported that 3 % of the world’s population is suffering from HCV infection that is about 170 million people. The prevalence of chronic HCV infections in Pakistan is about 5%, with very common individuals being infected with HCV genotype 3a prevalence is in the range of 4.1 to 36% reported from various parts of Khyber Pakhtunkhwa Province of Pakistan. This study was carried out in District Mardan Khyber Pakhtunkhwa. A total 1500 HCV suspected individuals visited District Headquarter hospital Mardan during September 2014 to April 2015 were enrolled. HCV antibodies were detected in about 230 patient serums during this screening. Out of these 230 patients 217 patient were further confirmed by qualitative Real Time PCR. All 217 samples were further analyzed for HCV genotyping by PCR based molecular technique. Genotyping results showed that HCV genotype 3a was found in 156 (72%) of the HCV positive isolates, 2a genotype in 22 (10%) and 3b genotype 17 (8%) and remaining 10% were mixed genotype. HCV genotype genotype 3a was declared as the most prevalent genotype with same in both genders that is 72 %. Genotypes 2a, 2b and 3b were more prevalent among male patients while mixed genotype was mostly observed in female infected individuals. Moreover majority of the infected population were form the age group 41-50 year. In 21-30 years age group the most prevalent genotype 3a after than following in competition 3b, in 31-40 years age group 2a 5 (7%), in years age group 41-50 2a 8 (9%) more prevalent. Keywords: Hepatitis C, Genotypes, Pakistan

Background: Pakistan is one of the world’s uppermost burdens of hepatitis C and B. Our research will assist to enhance and update preventative and treatment methods across the country. Methods: We screened 408 drug abusers for HBV and HCV in the medical and public health literature from study 1 June 2021 to 31 December 2021 on oral and injection drug users from Khyber Pakhtunkhwa Mardan District, Pakistan to evaluate the frequency of hepatitis B and C. Results: Out of 408 half of the individuals were screened for HCV-specific antibodies 204 and 204 for HBV surface antigen by a one-step rapid immune-chromatographic test. For all those who were screened for HCV antibodies, 171 individuals were negative and 30 individuals were positive and 14 % prevalence was observed in drug-addicted individuals. All those were screened for HBV surface antigen 161 individuals were negative and 43 % individuals were positive and 21 % prevalence was observed in drug addicted individuals. According to Age –wise distribution the high prevalence was found between 17-30 years Age 57 % and then followed by the 31-45 years age group having 28 % and the lowest HBV infection was observed in above 45 years Age group was only 15 %. Among HBV 43 positive individuals 70 % were drug abusers while the rest 30 % were oral drug users. In HCV 30 positive individuals 76 % were drug abusers while the rest 23 % were oral drug users. Among drug abusers, an injection drug user infectivity rate of 72 % was high as compared to oral drug abusers' 28 %. Conclusions: Our findings show that the prevalence of HCV and HBV is much higher among IDUs than in the overall population of Pakistan. Injecting drug users are at high risk of HBV and HCV infection transmission, and they can transfer diseases to the community through risky behavior such as syringe exchange and unsafe sex. As a result, various levels of prophylaxis are necessary for these fatal illnesses. Keywords: Drug abuser, Hepatitis B virus, Hepatitis C virus, Pakistan.

Introduction The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays. Methods In this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver-Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis-Menten kinetics. Results In AChE inhibitory assay, compounds 1 and 2 exhibited IC50 of 343.45 and 422.98 µM, respectively, against AChE enzyme. Similarly, both the compounds showed IC50 of 276.86 and 357.91 µM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC50 of 157.71 and 471.79 µM against α-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC50 values of 297.98, 332.94, and 825.92 µM against DPPH, ABTS, and H2O2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2. Conclusion Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.

Introduction The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays. Methods In this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver–Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis–Menten kinetics. Results In AChE inhibitory assay, compounds 1 and 2 exhibited IC50 of 343.45 and 422.98 µM, respectively, against AChE enzyme. Similarly, both the compounds showed IC50 of 276.86 and 357.91 µM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC50 of 157.71 and 471.79 µM against α-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC50 values of 297.98, 332.94, and 825.92 µM against DPPH, ABTS, and H2O2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2. Conclusion Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.

In recent years, drug discovery paradigm has been shifted from conventional single target inhibition toward multitarget design concept. In current research, we have reported synthesis, in-vitro, in-vivo and acute toxicity determination of N-substituted pyrrolidine-2,5-dione derivatives as multitarget anti-inflammatory agents. We synthesized cycloalkyl, alkyl and aryl carbonyl derivatives by the Michael addition of ketones to N-substituted maleimides using self-assembled three component system as an organocatalyst. Anti-inflammatory potential of the compounds was determined by using different in-vitro assays, like cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase, albumin denaturation and anti-protease assays. Amongst the synthesized compounds, 13a-e series of compounds showed inhibition in low micromolar to submicromolar ranges. These compounds also demonstrated COX-2 selectivity. Compound 13e with IC50 value 0.98 μM and SI of 31.5 emerged as the most potent inhibitor of COX-2. Based on in-vitro results, in-vivo anti-inflammatory investigations were performed on compounds 3b and 13e via carrageenan induced paw edema test. The possible mode of action of compounds 3b and 13e were ascertained with various mediators like histamine, bradykinin, prostaglandin and leukotriene. In-vivo acute toxicity study showed the safety of synthesized compounds up to 1000 mg/kg dose. The selectivity of the compounds against cyclooxygenase isoforms was supported by docking simulations. Selective COX-2 inhibitors showed significant interactions with the amino acid residues present in additional secondary COX-2 enzyme pocket. Furthermore, in-silico pharmacokinetic predictions confer the drug-like characteristics.