A Novel Inhibitor of DKK1/LRP6 Interactions Against the Alzheimer Disease: An Insilco Approach.

The activation of the Wnt signaling pathway is implicated in a neuroprotective mechanism against the Alzheimer disease. When this pathway is blocked, it activates GSK3 beta, leading to tau hyperphosphorylation and the apoptosis of neurons. Dickkopf-related protein 1 (DKK1) is a protein that competes with the Wnt ligand for the low-density lipoprotein receptor-related protein 6 (LRP6) receptor's binding, interrupting the Wnt-induced Fzd-Wnt-LRP6 complex. This counteracts Wnt's neuroprotective effect and contributes to the progression of the Alzheimer disease. The aim of this study was to use in silico approach to develop new agents that can combat the Alzheimer disease by targeting the interaction between DKK1 and LRP6. To achieve this, we conducted a virtual screening (Vsw) of the Asinex-CNS database library (n = 54 513) compounds against a generated grid in LRP6 protein. From this screening, we selected 6 compounds based on their docking score and performed molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations on the selected ligands. Next, we evaluated the Absorption, Distribution, Metabolism, and Excretion (ADME) results of the 6 screened compounds using the Quick prop module of Schrödinger. We then employed several computational techniques, including PCA (Principal Component Analysis), DCCM (Dynamic Cross-Correlation Map), molecular dynamics simulation, and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA)-based negative binding free energy (BFE) calculation, to further analyze the compounds. Our extensive computational analysis resulted in the identification of 3 potential hits, LAS 29757582, LAS 29984441, and LAS 29757942. These compounds were found to block the interaction of DKK1 with LRP6 (A and B interface) protein, and their potential as therapeutic agents was supported by negative BFE calculation. Therefore, these compounds show potential as possible therapeutic agents for treating the Alzheimer disease through targeting the interaction between DKK1 and LRP6.

Neutrophil-lymphocyte ratio as a predictor of adverse outcome in patients with community-acquired pneumonia: A systematic review.

Background: Community-acquired pneumonia (CAP) is the acute infection of lung tissue in an immunocompetent who acquired it from the community. Its incidence and mortality are significant and require a marker to predict the severity and mortality in these patients. Neutrophil-lymphocyte ratio (NLR) is a simple, cheap, and easy-to-use marker and this study describes its role in predicting the adverse outcome in patients with CAP. Methods: PubMed, EMBASE, and Google Scholar were used to search for related studies on February 8, 2021. A total of 186 articles were retrieved upon detailed searching in the databases and search engines. After a series of removing duplicate articles, title and abstract screening, and full-text review; nine articles were found eligible and included in the study. The data from each article were collected in MS Excel and the findings were summarized in this manuscript. Results: The total number of patients analyzed in this systematic review is 3340. The mean age of the patient in the included studies ranged from 61 to 90.4 years. All studies had adverse outcomes as the endpoint of the study, which included in-hospital mortality or intensive care unit (ICU) admission or deterioration from medium and low risk to high risk or 30 days' mortality. The prevalence of endpoint ranged from 5.8% to 44.8%. NLR with a cutoff value of more than 10 was shown to predict mortality compared to C-reactive protein levels, white blood cell count, neutrophil count, lymphocyte level, Pneumonia Severity Index (PSI) level, PSI class, procalcitonin, and CURB-65 (Confusion, Respiratory rate, Blood pressure, 65 years of age and older) in most of the studies. Conclusion: NLR is a simple, easily measured yet promising marker for predicting outcomes in patients with CAP.

IVIG plus Glucocorticoids versus IVIG Alone in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: A Systematic Review and Meta-Analysis.

Background: There is limited information available regarding the management of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2. We performed a systematic review and meta-analysis to evaluate the optimal treatment using IVIG alone versus IVIG plus glucocorticoids. Methods: PubMed, Google Scholar, EMBASE, and Cochrane databases were searched along with other secondary searches. Studies published within the time frame of January 2020 to August 2021 were included. We screened records, extracted data, and assessed the quality of the studies using NOS. Studies that directly compare the two treatment groups were included. Analyses were conducted using the random-effects model (DerSimonian-Laird analysis) if I 2 > 50% and fixed-effects model was used if I 2 < 50%. Results: We included three studies in the final quantitative analysis. The initial therapy with the IVIG plus glucocorticoids group significantly lowered the risk of treatment failure (OR 0.57, 95% CI (0.42, 0.79), I 2 45.36%) and the need for adjunctive immunomodulatory therapy (OR 0.27, 95% CI (0.20, 0.37), I 2 0.0%). The combination therapy showed no significant reduction in occurrence of left ventricular dysfunction (OR 0.79, 95% CI (0.34, 1.87), I 2 58.44%) and the need for inotropic support (OR 0.83, 95% CI (0.35, 1.99), I 2 75.40%). Conclusion: This study supports the use of IVIG with glucocorticoids compared to IVIG alone, as the combination therapy significantly lowered the risk of treatment failure and the need for adjunctive immunomodulatory therapy.

Kikuchi-Fujimoto disease: A rare case report from Nepal.

Clinicians and pathologists must be aware of the occurrence of Kikuchi-Fujimoto Disease, as one of the differential diagnoses of cervical lymphadenopathy.

Endogenous endophthalmitis and multifocal brain abscess-An interesting case.

We present an unusual case that staphylococcal brain abscess can present in an immunocompetent with endogenous endophthalmitis secondary to a septic foci and early prevention of dissemination with appropriate management to prevent its complications.

Congenital Partial Intercostal Liver Herniation.

Congenital intercostal liver herniation is a rare entity. The exact etiology of congenital intercostal liver herniation is unknown. Left sided intercostal herniation is even rarer. We present a case report of an eight-day old female who presented to the emergency department of Kanti Children's Hospital with tissue mass protruding through a defect in the left side of anterior chest wall since birth. Sonographic and radiological investigation revealed the tissue to be an extension of the part of the left lobe of the liver with decreased vascularity. There were no other congenital anomalies. Laparotomy with thoracotomy with resection of the non-viable herniated part and closure of defect was done. During postoperative period patient developed surgical site infection and wound dehiscence for which daily dressing and later secondary suturing was done. Keywords: Intercostal liver herniation.