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YTHDC1 (YTH domain containing 1), a crucial reader protein of N6-methyladenosine (m6A) mRNA, plays a critical role in various cellular functions and is considered a promising target for therapeutic intervention in acute myeloid leukemia and other cancers. In this study, we identified orthosteric small-molecule ligands for YTHDC1. Using a molecular docking approach, we screened the eMolecules database and recognized 15 top-ranked ligands. Subsequently, molecular dynamics simulations and MM/PBSA analysis were used to assess the stability and binding free energy of these potential hit compounds in complex with YTHDC1. Notably, five compounds with IDs of ZINC82121447, ZINC02170552, ZINC65274016, ZINC10763862, and ZINC02412146 exhibited high binding affinities and favorable binding free energies. The results also showed that these compounds formed strong hydrogen bonds with residues SER378, ASN363, and ASN367 and interacted with the aromatic cage of the YTHDC1 reader protein through TRP377, TRP428, and hydrophobic residue LEU439. To assess their viability as lead compounds, we conducted absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies to reveal promising features for these identified small molecules, shedding light on their pharmacokinetic and safety profiles. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of Intradermal Tranexamic acid and Intense Pulse Light (IPL) in the treatment of melasma. Study Design: Interventional study. Setting: Department of Dermatology, HIT Hospital. Period: Dec 2022 to May 2023. Material & Methods: 88 Female aged between 18 and 50 with melasma were included in this study. Participants who have used topical treatments for melasma, with any medical illness or bleeding disorder, history of photosensitivity were excluded. Participants of ITA group received intradermal tranexamic acid in a concentration of 4mg/ml monthly for four sessions. While the participants of IPL group were treated fortnightly for four sessions. mMASI was used to calculate the severity of melasma before and 2 weeks after last session. Patients perception of treatment efficacy and side effects were noted in each group. SPSS-28 was used. Paired t- test and independent t- test was applied to compare the effectiveness of both treatment modalities. A p-value ≤0.05 was considered as significant. Chi square was used to compare the side effects of both the groups. Results: Paired t-test indicated a highly significant p-value of less than 0.000 in both the groups. mMASI-II scores of both groups were compared using an independent t-test, p-value was found to be statistically insignificant at 0.512. Participants in ITA group experienced more side effects, comparison of side effects between both groups was done using chi-square test, and p-value was found to be statistically significant at 0.002. Conclusion: ITA and IPL have emerged as secure and efficacious therapeutic choices. [ABSTRACT FROM AUTHOR]

The Spike (S) protein of the SARS-CoV-2 virus that causes the COVID-19 disease is considered the most important target for vaccine, drug and therapeutic research as it attaches and binds to the ACE2 receptor of the host cells and allows the entry of this virus. Analysis and classification of newly determined S protein structures for SARS-CoV-2 are critical to properly understand their functional, evolutionary and architectural relatedness to already known protein structures. In this paper, first, the comparative analysis of SARS-CoV-2 S protein structures is performed. Through comparative analysis, the S protein structures in the PDB (protein data bank) database are compared and analyzed not only with each other but with the structures of other viruses for various parameters. Second, the S protein structures in PDB are classified into different variants, and the associated published literature is studied to investigate what kind of therapeutics (antibodies, T-cell receptors and small molecules) are used on the structures. This is the first study that classifies the S protein structures of the SARS-CoV-2 in PDB into various variants, and the obtained comparative analysis results could be beneficial to the research community, in general, and to crystallographers and health workers, in particular. [ABSTRACT FROM AUTHOR]

Objective: To compare oral Montelukast with oral Doxycycline in the treatment of moderate Acne Vulgaris in terms of mean change in acne severity index. Study Design: Quasi-experimental study. Place and Duration of Study: Department of Dermatology, Pak Emirates Military Hospital Rawalpindi, from Mar 2016 to Aug 2016. Methodology: A total of 84 patients were included in the study. They were randomly assigned to group A and B by consecutive non probability sampling technique. Group A was given 100mg Doxycycline with topical 10% benzoyl peroxide and group B was given 5mg Montelukast with topical 10% benzoyl peroxide. Acne severity index (ASI) was calculated at base line and after one month. Mean change in acne severity index was observed for both the groups. Results: Independent sample t-test was used to compare the means. Mean post treatment change in acne severity index of group A was 5.45 ± 1.29 and group B was 1.80 ± .59 respectively (p-value <0.001). On post stratification analysis for age and gender results were consistent. Conclusion: Efficacy of Doxycycline is significantly better in terms of mean change in Acne Severity Index, as compared to Montelukast. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical outcome of fixation of anterior cruciate ligament avulsion injuries in Military Soldiers. Study Design: Descriptive case series. Place and Duration of Study: Orthopedic department, Combined Military Hospital (CMH) Rawalpindi, from Jun 2015 to Jun 2016. Material and Methods: Open reduction and screw fixation was done in 30 soldiers presenting with McKeever type III and IV avulsion fractures of anterior cruciate ligament. Outcome evaluation was carried out at 3 and 6 months. Lachman test was used for stability. Standard AP and Lateralx-rayswere taken to monitor bony healing. Lysholm score was used for functional evaluation. Results: All 30 patients showed complete healing at 3 months. Three patients revealed residual laxity. Mean extension loss was 5 degrees. Lysholm score improved from pre-operative mean of 29.97 (SD ± 5.46) to postoperative mean of 95.67 (SD ± 1.47). Conclusion: This study demonstrated operative fixation of Grade III and IV anterior cruciate ligament avulsion injuries as a successful surgical option in Military soldiers. [ABSTRACT FROM AUTHOR]

The current study evaluated the effect of virtual reality based balance training in 30 stroke patients recruited via purposive sampling technique for a clinical trial. Sealed envelope method was used to randomly allocate patients into two groups, i.e. Exer-gaming group (EGG) (n=15) and traditional training (TBT) group (n=15). Patients ranging in age from 50 to 60 years were included using Modified Rankin Scale (MRS). Patients with cognitive deficits, severe physical impairments, contractures, inability to perform tasks, complications of the joint that affected movement, history of recent fracture, arthritis and those on drugs that could affect their physical function were excluded. Data was collected using Berg Balance Scale (BBS) and Timed Up & Go Test (TUG). Significant improvement was observed in the exer-gaming training group after completing intervention (P<0.001). Exer-gaming appears to be more effective in improving functional level, mobility and balance in stroke patients. The study also suggests that exer-gaming further provides dynamic environment for stroke patients, thereby improving dynamic balance and mobility.