Effect of constraint-induced movement therapy in reducing severity of mirror movements in children with unilateral spastic cerebral palsy.

To determine the effec t of constraint-induced movement therapy (CIMT ) in improving hand function and reduction in severity of mirror movements in children with unilateral spastic cerebral palsy who have mirror movement disorder. Spastic hemiplegic CP children of either gender, aged 6 to 16 years, with mirror movements of grade 1 and 2 who were able to make a gross grip, were included in this single arm feasibility study. CIMT was provided as an intervention to these children for six hours per day for 15 consecutive week days. Woods and Teuber criteria was applied for the assessment of mirror m oveme nt s. Pre - and po stinte rventi on assess ment results showed that there was improvemen t in the unimanual and bimanual hand func tion in CP-affected children (p<0.05) and reduction in the severity of mirror movements ( p<0 .05). Constra intinduced movement therapy improved hand function and reduced the severity of mirror movements in children with unilateral spastic cerebral palsy.

Evaluating ionic liquids for its potential as eco-friendly solvents for naproxen removal from water sources using COSMO-RS: Computational and experimental validation.

An emerging contaminant of concern in aqueous streams is naproxen. Due to its poor solubility, non-biodegradability, and pharmaceutically active nature, the separation is challenging. Conventional solvents employed for naproxen are toxic and harmful. Ionic liquids (ILs) have attracted great attention as greener solubilizing and separating agent for various pharmaceuticals. ILs have found extensive usage as solvents in nanotechnological processes involving enzymatic reactions and whole cells. The employment of ILs can enhance the effectiveness and productivity of such bioprocesses. To avoid cumbersome experimental screening, in this study, conductor like screening model for real solvents (COSMO-RS) was used to screen ILs. Thirty anions and eight cations from various families were chosen. Activity coefficient at infinite dilution, capacity, selectivity, performance index, molecular interactions using σ-profiles and interaction energies were used to make predictions about solubility. According to the findings, quaternary ammonium cations, highly electronegative, and food-grade anions will form excellent ionic liquid combinations for solubilizing naproxen and hence will be better separating agents. This research will contribute easy designing of ionic liquid-based separation technologies for naproxen. In different separation technologies, ionic liquids can be employed as extractants, carriers, adsorbents, and absorbents.

Genetic diversity and haplotypes of Echinococcus granulosus isolated from cattle and buffaloes and first report of E. ortleppi (G5) in buffaloes in Pakistan based on mitochondrial cytochrome c oxidase subunit-1 gene (mt-CO1) markers.

Cystic echinococcosis (CE) is a parasitic disease that is caused by larval stage of Echinococcus granulosus tapeworm, one of the most important and neglected zoonotic disease. Although the echinococcosis is endemic in the neighboring countries, information regarding circulating genotypes of E. granulosus sensu lato is scarce in Pakistan. Therefore, the main purpose of this report was to contribute in molecular epidemiology and to find genetic variation and haplotypes of E. granulosus s.l. in cattle and buffalo isolates. To identify species circulating in country, parasite samples were collected from different slaughterhouses and butcher shops of two major cities, Rawalpindi and Peshawar located in Punjab and Khyber Pakhtunkhwa (KP) provinces, Pakistan, respectively. A total of 100 CE cyst samples were investigated from buffalo (n = 61), and cattle (n = 39) hosts. After genomic DNA extraction from individual cyst materials, mt-CO1 (875 bp) gene was amplified by PCR. After that, PCR products were electrophoresed on the agarose gel then purified and sequenced using forward primer. The sequences were trimmed (779 bp), aligned and matched with NCBI published sequences. E. granulosus s.s. (G1, G3) (71.4%; n = 20/28) was confirmed as the dominant species in buffalo and cattle. E. ortleppi (G5) (28.6%; n = 8/28) was recorded for the first time in both buffalo and cattle isolates from Rawalpindi. E. granulosus s.l. haplotype network showed single predominant haplotype, which comprised 40% of population. Tajima's D and Fu's Fs were negative and significant for E. ortleppi (G5), suggesting population expansion in Pakistan. Therefore, more studies using isolates of E. granulosus s.l. from various locations and intermediate hosts across Pakistan will add new data on molecular epidemiology and genotyping for effective control strategies of CE in Pakistan.

Ionic Liquid-Based Green Emulsion Liquid Membrane for the Extraction of the Poorly Soluble Drug Ibuprofen.

Ibuprofen (Ibf) is a biologically active drug (BADs) and an emerging contaminant of concern (CECs) in aqueous streams. Due to its adverse effects upon aquatic organisms and humans, the removal and recovery of Ibf are essential. Usually, conventional solvents are employed for the separation and recovery of ibuprofen. Due to environmental limitations, alternative green extracting agents need to be explored. Ionic liquids (ILs), emerging and greener alternatives, can also serve this purpose. It is essential to explore ILs that are effective for recovering ibuprofen, among millions of ILs. The conductor-like screening model for real solvents (COSMO-RS) is an efficient tool that can be used to screen ILs specifically for ibuprofen extraction. The main objective of this work was to identify the best IL for the extraction of ibuprofen. A total of 152 different cation-anion combinations consisting of eight aromatic and non-aromatic cations and nineteen anions were screened. The evaluation was based upon activity coefficients, capacity, and selectivity values. Furthermore, the effect of alkyl chain length was studied. The results suggest that quaternary ammonium (cation) and sulfate (anion) have better extraction ability for ibuprofen than the other combinations tested. An ionic liquid-based green emulsion liquid membrane (ILGELM) was developed using the selected ionic liquid as the extractant, sunflower oil as the diluent, Span 80 as the surfactant, and NaOH as the stripping agent. Experimental verification was carried out using the ILGELM. The experimental results indicated that the predicted COSMO-RS and the experimental results were in good agreement. The proposed IL-based GELM is highly effective for the removal and recovery of ibuprofen.

Breast Cancer Management Consensus By The Society of Surgeons and Surgical Oncology Society of Pakistan.

The Society of Surgeons of Pakistan and The Society of Surgical Oncology of Pakistan with factions from various major centres comprising of surgical oncology, medical and radiation oncology collaborated to reach consensus on breast cancer management guidelines and a framework of "good practice" minimum standards of care. The aim of the task force was to enhance treatment standards, which have a direct correlation with improving patient mortality and morbidity and long-term survival whilst taking into consideration economic limitations of access to leading centers of excellence as well as minimum expertise required in health care. These multidisciplinary guidelines, whilst not exhaustive, aim to provide an algorithm of care for breast cancer patients at tertiary care centres and district level hospitals to provide most appropriate treatment.

Blockchain technology for agricultural supply chains during the COVID-19 pandemic: Benefits and cleaner solutions.

This study aims to investigate blockchain technology for agricultural supply chains during the COVID-19 pandemic. Benefits and solutions are identified for the smooth conduction of agricultural supply chains during COVID-19 using blockchain. This study uses interviews with agricultural companies operating in Pakistan. The findings discover the seven most commonly shared benefits of applying blockchain technology, four major challenges, and promising solutions. About 100% of the respondents mentioned blockchain as a solution for tracking the shipment during COVID-19, data retrieval and data management, product and transaction frauds, and an Inflexible international supply chain. Roughly 75% of the respondents mentioned the challenge of lack of data retrieval and data management and the Inflexible international supply chain in COVID-19 besides their solutions. This study can expand existing knowledge related to agricultural supply chains. The experiences shared in this study can serve as lessons for practitioners to adopt the blockchain technology for performing agricultural supply chain during pandemic situations such as COVID-19.

Association between handgrip strength and maximum expiratory flow with site-specific bone mineral density of healthy young adults.

OBJECTIVE: To explore the association of handgrip strength and peak expiratory flow rate with site-specific bone mineral density T scores, and to study the correlation of body mass index and physical activity with the three parameters. METHODS: The cross-sectional study was conducted in November 2018 at the Combined Military Hospital, Lahore Medical College and Institute of Dentistry, Lahore, Pakistan, and comprised healthy young adults. Data was collected using the international physical activity questionnaire. The subjects were grouped into low, moderate and high categories. Handgrip strength, peak expiratory flow rate, bone mineral density T scores and body mass index were measured for each subject. Data was analysed using SPSS 24. RESULTS: Of the 102 subjects, 52(50.9%) were males and 50(49%) were females. There was a significant difference between the median values for all parameters of males and females (p<0.05). Bone mineral density and physical activity were moderately associated with handgrip strength and peak expiratory flow rate (p<0.05). Body mass index showed a moderate association with bone mineral density (p<0.05). CONCLUSIONS: Healthy young adults with better respiratory function and handgrip strength were found to have higher values of site-specific calcaneal bone mineral density. Subjects with higher reported levels of physical activity and a higher body mass index within a healthy range presented with improved values of bone mineral density, handgrip strength and peak expiratory flow rate.

E-Learning amid the COVID-19 Lockdown: Standpoint of Medical and Dental Undergraduates.

BACKGROUND AND OBJECTIVE: The corona-virus (COVID-19) pandemic has had devastating impacts on not only the health and socio-economic conditions but also on the education sector in various countries. Consequently, the world of education entered a new era of E-learning. This descriptive study, thus, aims to evaluate the standpoint of medical and dental undergraduates regarding E-learning amid the Covid-19 lockdown. METHODS: A descriptive online questionnaire was used to gather responses via Google forms. The questionnaire consisted of questions categorized as technology access, online skills and relationships, students' views, and student's perception of possible advantages of E-learning. Two hundred and eighty three medical and dental students of CMH Lahore Medical College participated in the study. RESULTS: One hundred and seventy nine female and 104 male students responded to the questionnaire. The results of the study showed students encouraging the accommodation of E-learning into current teaching practices. Students agreed online study material not only provides flexibility in the learning process (p=0.003) but also saves time (p = 0.012). Female participants showed a more positive readiness response towards e learning than males (p =0.001). Results also showed students have easier access to online teaching resources. Regarding online lectures, the students believe that online lectures were more organized (p= 0.001) and stimulated student interest (p=0.026). Students believe that frequent participation in the learning process is important for success in online education (p=0.002). CONCLUSION: Undergraduate medical and dental students from the said private medical college are well equipped and ready to shift towards online education.

Schiff bases of tryptamine as potent inhibitors of nucleoside triphosphate diphosphohydrolases (NTPDases): Structure-activity relationship.

Overexpression of NTPDases leads to a number of pathological situations such as thrombosis, and cancer. Thus, effective inhibitors are required to combat these pathological situations. Different classes of NTPDase inhibitors are reported so far including nucleotides and their derivatives, sulfonated dyes such as reactive blue 2, suramin and its derivatives, and polyoxomatalates (POMs). Suramin is a well-known and potent NTPDase inhibitor, nonetheless, a range of side effects are also associated with it. Reactive blue 2 also had non-specific side effects that become apparent at high concentrations. In addition, most of the NTPDase inhibitors are high molecular weight compounds, always required tedious chemical steps to synthesize. Hence, there is still need to explore novel, low molecular weight, easy to synthesize, and potent NTPDase inhibitors. Keeping in mind the known NTPDase inhibitors with imine functionality and nitrogen heterocycles, Schiff bases of tryptamine, 1-26, were synthesized and characterized by spectroscopic techniques such as EI-MS, HREI-MS, 1H-, and 13C NMR. All the synthetic compounds were evaluated for the inhibitory avidity against activities of three major isoforms of NTPDases: NTPDase-1, NTPDase-3, and NTPDase-8. Cumulatively, eighteen compounds were found to show potent inhibition (Ki = 0.0200-0.350 µM) of NTPDase-1, twelve (Ki = 0.071-1.060 µM) of NTPDase-3, and fifteen compounds inhibited (Ki = 0.0700-4.03 µM) NTPDase-8 activity. As a comparison, the Kis of the standard inhibitor suramin were 1.260 ±â€¯0.007, 6.39 ±â€¯0.89 and 1.180 ±â€¯0.002 µM, respectively. Kinetic studies were performed on lead compounds (6, 5, and 21) with human (h-) NTPDase-1, -3, and -8, and Lineweaver-Burk plot analysis showed that they were all competitive inhibitors. In silico study was conducted on compound 6 that showed the highest level of inhibition of NTPDase-1 to understand the binding mode in the active site of the enzyme.

2D:4D digit ratios in males and females and its correlation with simple reaction time: A cross sectional Study at Combined Military Hospital (CMH), Lahore, Pakistan.

A cross-sectional study was conducted on 86 medical students between the ages of 18 to 25 years studying at the Combined Military Hospital (CMH) in Lahore, Pakistan. They were assessed for height, weight, digit length of the 2nd and 4th fingers of both hands and reaction time (response time to auditory stimulus as measured by BIOPAC). Of the 86 students, 42 (49%) were male and 44 (51%) were female, with a mean age of 19.55±1.017 and 19.86±0.905 years, respectively. There was a significant difference in the height, weight and Body Mass Index (BMI) of the students. The mean 2D:4D ratio for males on the left hand was 0.958±0.029 and for females it was 0.979±0.363 (p=0.004). The ratio for the right hand for males was 0.958±0.031 and for the females it was 0.977±0.035 (p=0.011). There was a significant correlation between the 2D: 4D ratio in the left hand with the reaction time in the dominant hand at random intervals (r= -0.240, p= 0.027) and with reaction time in the non-dominant hand at fixed intervals (r= -0.232, p= 0.03). Our results concluded that there is a negative correlation between the digit ratio and the reaction time. Those individuals who had lower digit ratios had faster reaction times than those who had higher digit ratios.

Experimental platform utilising melting curve technology for detection of mutations in Mycobacterium tuberculosis isolates.

Tuberculosis (TB) remains one of the most deadly infections with approximately a quarter of cases not being identified and/or treated mainly due to a lack of resources. Rapid detection of TB or drug-resistant TB enables timely adequate treatment and is a cornerstone of effective TB management. We evaluated the analytical performance of a single-tube assay for multidrug-resistant TB (MDR-TB) on an experimental platform utilising RT-PCR and melting curve analysis that could potentially be operated as a point-of-care (PoC) test in resource-constrained settings with a high burden of TB. Firstly, we developed and evaluated the prototype MDR-TB assay using specimens extracted from well-characterised TB isolates with a variety of distinct rifampicin and isoniazid resistance conferring mutations and nontuberculous Mycobacteria (NTM) strains. Secondly, we validated the experimental platform using 98 clinical sputum samples from pulmonary TB patients collected in high MDR-TB settings. The sensitivity of the platform for TB detection in clinical specimens was 75% for smear-negative and 92.6% for smear-positive sputum samples. The sensitivity of detection for rifampicin and isoniazid resistance was 88.9 and 96.0% and specificity was 87.5 and 100%, respectively. Observed limitations in sensitivity and specificity could be resolved by adjusting the sample preparation methodology and melting curve recognition algorithm. Overall technology could be considered a promising PoC methodology especially in resource-constrained settings based on its combined accuracy, convenience, simplicity, speed, and cost characteristics.

Phytochemical and Biological Activities of Pseudocalymma elegans: A False Garlic.

Evaluation of phytochemical constituents and antioxidant and antimicrobial activities of hexane (PELH), dichloromethane (PELDCM), ethyl acetate (PELEA), and MeOH (PELM) extracts of young leaves of Pseudocalymma elegans have been carried out. Moreover, extracts have also been explored for the presence of sulphur containing compounds, 1,2-dithiolane (33), diallyl disulfide (35), 3-vinyl-1,2-dithiacyclohex-5-ene (37), and diallyl trisulfide (38) responsible for the garlic like smell of P. elegans. All the extracts were found to be antioxidant and showed potent inhibition with IC50 values of 0.168 ± 0.001, 0.128 ± 0.002, 0.221 ± 0.011, and 0.054 ± 0.001, respectively, as compared to standard drugs ascorbic acid (AA) and butylated hydroxytoluene (BHT). The ethyl acetate extract (PELE) showed excellent activities against few Gram-positive and Gram-negative bacteria and some fungi as compared with standard drug ceftriaxone (3rd generation cephalosporin) and nystatin, respectively. Chemical constituents of hexane, dichloromethane, and ethyl acetate extracts were identified by gas chromatography-mass spectrometry and mass spectral library search. Over all 55 chemical constituents were first time identified from the leaves which included branched and n-hydrocarbons, fatty acids, fatty acid methyl esters, fatty alcohols, terpenes, alkaloid, vitamins, glycosides, aromatic compounds, and sulfur containing compounds. Two known chemical constituents, ursolic acid (1) and ß-amyrin (2), were also purified for the first time from the MeOH extract. To elucidate the structures of these compounds, UV, IR, EI-MS, 1 H- and 13 C-NMR spectroscopy were used.

In silico identification of promiscuous scaffolds as potential inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase for treatment of Falciparum malaria.

CONTEXT: Malaria remains one of the prevalent infectious diseases worldwide. Plasmodium falciparum 1-deoxy-d-xylulose-5-phosphate reductoisomerase (PfDXR) plays a role in isoprenoid biosynthesis in the malaria parasite, making this parasite enzyme an attractive target for antimalarial drug design. Fosmidomycin is a promising DXR inhibitor, which showed safety as well as efficacy against Plasmodium falciparum malaria in clinical trials. However, due to its poor oral bioavailability and non-drug-like properties, the focus of medicinal chemists is to develop inhibitors with improved pharmacological properties. OBJECTIVE: This study described the computational design of new and potent inhibitors for deoxyxylulose 5-phosphate reductoisomerase and the prediction of their pharmacokinetic and pharmacodynamic properties. MATERIAL AND METHODS: A complex-based pharmacophore model was generated from the complex X-ray crystallographic structure of PfDXR using MOE (Molecular Operating Environment). Furthermore, MOE-Dock was used as docking software to predict the binding modes of hits and target enzyme. RESULTS: Finally, 14 compounds were selected as new and potent inhibitors of PfDXR on the basis of pharmacophore mapping, docking score, binding energy and binding interactions with the active site residues of the target protein. The predicted pharmacokinetic properties showed improved permeability by efficiently crossing blood-brain barrier. While, in silico promiscuity binding data revealed that these hits also have the ability to bind with other P. falciparum drug targets. DISCUSSION AND CONCLUSION: In conclusion, innovative scaffolds with novel modes of action, improved efficacy and acceptable physiochemical/pharmacokinetic properties were computationally identified.

Synthesis, ß-glucuronidase inhibition and molecular docking studies of hybrid bisindole-thiosemicarbazides analogs.

Hybrid bisindole-thiosemicarbazides analogs (1-18) were synthesized and screened for ß-glucuronidase activity. All compounds showed varied degree of ß-glucuronidase inhibitory potential when compared with standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25µM). Compounds 4, 7, 9, 6, 5, 12, 17 and 18 showed exceptional ß-glucuronidase inhibition with IC50 values ranging from 0.1 to 5.7µM. Compounds 1, 3, 8, 16, 13, 2 and 14 also showed better activities than standard with IC50 values ranging from 7.12 to 15.0µM. The remaining compounds 10, 11, and 15 showed good inhibitory potential with IC50 values 33.2±0.75, 21.4±0.30 and 28.12±0.25µM respectively. Molecular docking studies were carried out to confirm the binding interaction of the compounds.

Breast cancer treatment in high-risk elderly patients: A challenging situation and difficult decisions.

OBJECTIVE: To assess whether high-risk elderly patients with aggressive tumour biology can be offered standard treatment despite having multiple comorbid conditions. METHODS: This retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data of breast cancer patients aged 65 years or above treated between 2006 and 2012,. Data was collected regarding patients' demographics, baseline clinical characteristics, comorbidities, treatment and outcomes. Stata 12 was used for data analysis. RESULTS: Of the 407 patients in the study, 399(98%) were women and 8(2%) were men. The overall mean age at diagnosis was 70±4.9 years (range: 65-90 years). Overall, 59(14.5%) participants had family history of breast cancer. Bilateral disease was seen in 17(4.2%). Invasive ductal carcinoma was seen in 299(73.5%). Besides, 101(24.8%) patients had no comorbid conditions, while 138(34%) had one, 102(25%) had two and 66(16%) had three or more comorbid conditions. There was no statistically significant difference between those receiving standard treatment including surgery or other modalities. CONCLUSIONS: Elderly patients of breast cancer may be offered treatment according to the tumour biology and their overall functional status.

Foriegn Body In Rectum: An Unusual Case.

Rectal Foreign bodies have been reported in literature since long. They are inserted as a result of erotic behaviour. Rectal foreign bodies may be inserted as a result of sexual perversion or for nonsexual reasons such as constipation, concealment or in psychiatric patients1.Their insertion may be voluntary or involuntary as in impalement. Usually patients are men in their 40's but it shows a bimodal distribution from teenage up to 80's or 90's. Presentation is usually late due to embarrassment. They can be diagnosed by simple plain radiographs and digital rectal examination. Most of times they can be extracted per rectally after analgesia or general anaesthesia with laparotomy required only for perforation and peritonitis. Here we report a case of a 50 years old man who presented with a steel rod in rectum which was pulled out per rectally.

Role of oxidative injury in affecting the foetal & placental weights on exposure to tobacco smoke.

OBJECTIVE: To investigate the role of oxidative injury in affecting foetal and placental weights in mice by exposing them to tobacco smoke with or without supplementation with antioxidants. METHODS: The randomized control trial of pregnant mice at day one of gestation was conducted at Anatomy Department CPSP Regional Center Islamabad, from March 2005 to October 2005. The mice were divided into three groups: Group C had controls, while the two other groups, groups S and SV were exposed to secondary tobacco smoke in a whole body exposure chamber with and without supplementation with vitamins respectively. At term, the animals were sacrificed and the placentae and foetuses were weighed. The average values were calculated. The means for each group were analysed and the foetal placental ratio was calculated. SPSS 17 was used for statistical analysis. RESULTS: There were 44 mice; 15(34%) each in S and SV groups, while Group C had 14(32%) mice who acted as the controls. The mean foetal weight in Group S was 0.65±0.52g which was significantly less (p<0.0001) than1.48±0.19g in Group C. The mean foetal weight in Group SV was 0.97±0.65g which was not significantly different from S (p=0.124). The mean placental weight in Group S was 0.16±0.02g which was significantly less than 0.21±0.05gin Group C (p=0.014). In Group SV it was significantly more than Group S (p<0.0001). The ratio of mean foetal and mean placental weights in the groups C, S and SV were 7.05, 3.92 and4.41 respectively. CONCLUSIONS: Prenatal exposure to tobacco smoke decreased the mean foetal and placental weights and the foetal-placental ratio. This may partly be attributed to oxidative injury induced by free radicals in the tobacco smoke as it is prevented to some extent by simultaneous administration of antioxidants.

Approved treatments for neovascular age-related macular degeneration: current safety and future directions.

INTRODUCTION: Age-related macular degeneration (AMD) is a progressive retinal degenerative disease that is implicated as one of the leading causes of visual impairment in the elderly population. Vascular endothelial growth factor (VEGF) has been identified as the main driver of AMD, and various therapeutics have revolutionized the treatment and management of neovascular AMD (nAMD) with favorable visual and anatomical outcomes. AREAS COVERED: Physicians have a variety of approved therapeutics in their arsenal for patients with varying disease progression and patient-specific needs, with the ultimate goal of achieving optimal visual and anatomic outcomes. The literature search was conducted using PubMed, Google Scholar, and sources from companies' websites, allowing us to locate findings recently presented at conferences. EXPERT OPINION: Scientific advancements in the field have led to newly approved therapeutics and devices, such as the port-delivery system with ranibizumab (PDS), and further investigation is ongoing in the realm of gene therapy for retinal diseases. In addition to efficacy and durability, newer agents must have comparable safety profiles to older agents in order to be used broadly. These options introduce a level of complexity in nAMD treatment; however, physicians to personalize treatment to improve vision in nAMD patients and reduce treatment burden overall.

Laparoscopic excision of a large retroperitoneal cyst: Case report and literature review.

Retroperitoneal cysts, a rare surgical phenomenon, present diagnostic challenges due to their typically asymptomatic nature. A 62-year-old male presented with a 4-month history of abdominal distension and increased burping. Upon clinical examination, a soft, distended, nontender abdomen with a palpable mass extending from the epigastric region to 3 cm below the umbilicus was revealed. Imaging revealed a 14.6 cm × 15.8 cm × 16.4 cm nonenhancing retroperitoneal lesion, compressing the right ureter and causing mild right hydronephrosis. Multiple gall bladder calculi, an umbilical hernia, and lipomatous lesions associated with adrenal glands were also discovered. Laparoscopic retroperitoneal cystectomy, cholecystectomy, and umbilical hernia repair were performed. Intraoperatively, 150 ml ascitic fluid and 1200 ml cystic fluid were found. This case highlights the intricate clinical presentation of a retroperitoneal cyst, emphasizing the need for surgical exploration. Successful laparoscopic management contributes to the evolving understanding of optimal treatment strategies.

Identification of Novel Antileishmanial Chemotypes By High-Throughput Virtual and In Vitro Screening.

BACKGROUND: Leishmaniasis is a deadly protozoan parasitic disease and a significant health problem in underdeveloped and developing countries. The global spread of the parasite, coupled with the emergence of drug resistance and severe side effects associated with existing treatments, has necessitated the identification of new and potential drugs. OBJECTIVE: This study aimed to identify promising compounds for the treatment of leishmaniasis by targeting two essential enzymes of Leishmania donovani: trypanothione reductase (Try-R) and trypanothione synthetase (Try-S). METHODS: High-throughput virtual and in vitro screening of in-house and commercial databases was conducted. A pharmacophore model with seven features was developed and validated using the Guner-Henery method. The pharmacophore-based virtual screening yielded 690 hits, which were further filtered through Lipinski's rule, ADMET analysis, and molecular docking against Try-R and Try-S. Molecular dynamics studies were performed on selected compounds, and in vitro experiments were conducted to evaluate their activity against the promastigote and amastigote forms of L. donovani. RESULTS: The virtual screening and subsequent analysis identified 33 promising compounds. Molecular dynamics studies of two compounds (comp-1 and comp-2) demonstrated stable binding interactions with the target enzymes and high affinity. In vitro experiments revealed that 13 compounds exhibited moderate activity against both the promastigote (IC50, 41 µM-76 µM) and the amastigote (IC50, 44 µM-72 µM) forms of L. donovani. Compounds 1 and 2 showed the highest percent inhibition and the lowest IC50 values. CONCLUSION: The identified compounds demonstrated significant inhibitory activity against Leishmania donovani and stable interactions with target enzymes. These findings suggest that the compounds could serve as promising leads for developing new treatments for leishmaniasis.