IntroductionPancytopenia is a common presentation in the pediatric population. It is a manifestation of various diseases, and its etiology can be explained on the basis of bone marrow examination. The study aims to determine the etiological factors leading to pancytopenia via bone marrow examination in pediatric patients presenting in our hospital.Materials and methodsThis retrospective cross-sectional study was conducted in the Department of Pathology at a public sector tertiary care hospital. Data were recorded by convenience sampling from the patients’ database from January 2015 to April 2018. Patients aged 2 months to 15 years who had pancytopenia on peripheral blood smear and were admitted for bone marrow examination were included in the study. Patients who were beyond these age limits, diagnosed cases of aplastic anemia and leukemia, and those with a recent history of blood transfusion were excluded from the study. The analysis was done via the Statistical Package for Social Sciences (SPSS) v.23.0 (IBM SPSS Statistics, Armonk, NY, USA), and descriptive statistics were applied.ResultsOf 115 cases, 58 (50.4%) were males and 57 (49.6%) were females. Megaloblastic anemia was present in 32 (27.8%) patients, and it was the most common cause of pancytopenia. Non-malignant disorders were seen in 95 cases (82.6%) and malignant disorders were seen in 20 (17.4%) cases.ConclusionMegaloblastic anemia is the most common cause, and acute lymphoblastic leukemia is the most common malignant cause of pancytopenia in children. There was no significant gender predilection among causes of pancytopenia.
Because of the essential role of PLpro in the regulation of replication and dysregulation of the host immune sensing, it is considered a therapeutic target for novel drug development.To reduce the risk of immune evasion and vaccine effectiveness, small molecular therapeutics are the best complementary approach. Hence, we used a structure-based drug-designing approach to identify potential small molecular inhibitors for PLpro of SARS-CoV-2. Initial scoring and re-scoring of the best hits revealed that three compounds NPC320891 (2,2-Dihydroxyindene-1,3-Dione), NPC474594 (Isonarciclasine), and NPC474595 (7-Deoxyisonarciclasine) exhibit higher docking scores than the control GRL0617. Investigation of the binding modes revealed that alongside the essential contacts, i.e., Asp164, Glu167, Tyr264, and Gln269, these molecules also target Lys157 and Tyr268 residues in the active site. Moreover, molecular simulation demonstrated that the reported top hits also possess stable dynamics and structural packing. Furthermore, the residues' flexibility revealed that all the complexes demonstrated higher flexibility in the regions 120-140, 160-180, and 205-215. The 120-140 and 160-180 lie in the finger region of PLpro, which may open/close during the simulation to cover the active site and push the ligand inside. In addition, the total binding free energy was reported to be − 32.65 ± 0.17 kcal/mol for the GRL0617-PLpro, for the NPC320891-PLpro complex, the TBE was − 35.58 ± 0.14 kcal/ mol, for the NPC474594-PLpro, the TBE was − 43.72 ± 0.22 kcal/mol, while for NPC474595-PLpro complex, the TBE was calculated to be − 41.61 ± 0.20 kcal/mol, respectively. Clustering of the protein's motion and FEL further revealed that in NPC474594 and NPC474595 complexes, the drug was seen to have moved inside the binding cavity along with the loop in the palm region harboring the catalytic triad, thus justifying the higher binding of these two molecules particularly. In conclusion, the overall results reflect favorable binding of the identified hits strongly than the control drug, thus demanding in vitro and in vivo validation for clinical purposes.
Introduction: The World Health Organization (WHO) declared Covid-19 as a pandemic on March 11, 2020. Not only that the COVID-19 pandemic has brought the world to a complete lockdown but also burdened healthcare systems across the world immensely. Objective: In this paper, we discuss the different strategies we adopted in the Orthopaedics Department of District Head Quarter [DHQ] hospital Rawalpindi, during this ongoing pandemic and share our experience of successfully but cautiously providing orthopedic services to patients in a public hospital. We compare our workload and output of May 2020 [pandemic phase] to May 2019 [standard/normal phase]. Methodology: The Hospital policy was changed after the COVID-19 pandemic. We increased public awareness and reduced load in the OPD using different strategies. We postponed all elective cases; focusing our logistics and resources only on the patients in urgent need of surgical management. A minimum number of doctors and OTAs were allocated on each list. Inwards, the patient stay was reduced. As a standard PCR test for COVID-19 was expensive, we devised our screening through history, examination, and routine investigations. Results: The average stay inwards was reduced from 6.4±4.6 days in May 2019 to 2.7±3.6 days in May 2020. The decrease in the stay was statistically significant (p=.0206) and was associated with a 24.4% increase in the number of total patient admissions in May 2020 (n=56) as compared to May 2019 (n=45). The number of surgeries performed month to month was very similar in normal and pandemic periods. Our OPD patient attendance dropped from 200-250 patients per day in 2019 to 60-70 during the ongoing pandemic phase. Conclusion: We believe that sharing experiences between health care actors allows us to develop an effective strategy to provide the very best care to our patients during the COVID-19 pandemic.
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