Search

Biomolecules of marine origin have many applications in the field of biotechnology and medicine, but still hold great potential as bioactive substances against different diseases. The purification or total synthesis of marine metabolites is expensive, and requires a reliable selection method to reveal their pharmaceutical potential prior to clinical validation. This study aimed to explore the hidden potential of natural products from the gorgonian genus Antillogorgia as anti-SARS-CoV-2 agents, via binding affinity assessments and molecular dynamics (MDs) simulations. The three-dimensional protein structures of the nsp16–nsp10 complex, nsp13, and nsp14 were acquired from the RCSB PDB database. All 165 natural products (NPs) were discovered using the PubChem, ChemSpider, and CMNPD databases. The freeware Autodock Vina was used to conduct the molecular docking procedure, once the proteins and ligands were prepared using BIOVIA discovery studio and Avogadro software v1.95. Before running MDs simulations using the CABS-flex 2.0 website, the binding affinity assessments and amino acid interactions were carefully examined. Just twelve NPs were selected, and five of those NPs interacted optimally with the catalytic amino acids of proteins. To conclude, pseudopterosin A (−8.0 kcal/mol), seco-pseudopterosin A (−7.2 kcal/mol), sandresolide B (−6.2 kcal/mol), elisabatin A (−7.0 kcal/mol), and elisapterosin A (−10.7 kcal/mol) appeared to be the most promising candidates against the nsp16–nsp10, nsp13, and nsp14 proteins.

The world is already facing the devastating effects of the SARS-CoV-2 pandemic. A disseminated mucormycosis epidemic emerged to worsen this situation, causing havoc, especially in India. This research aimed to perform a multitargeted docking study of marine-sponge-origin bioactive compounds against mucormycosis. Information on proven drug targets and marine sponge compounds was obtained via a literature search. A total of seven different targets were selected. Thirty-five compounds were chosen using the PASS online program. For homology modeling and molecular docking, FASTA sequences and 3D structures for protein targets were retrieved from NCBI and PDB databases. Autodock Vina in PyRx 0.8 was used for docking studies. Further, molecular dynamics simulations were performed using the IMODS server for top-ranked docked complexes. Moreover, the drug-like properties and toxicity analyses were performed using Lipinski parameters in Swiss-ADME, OSIRIS, ProTox-II, pkCSM, and StopTox servers. The results indicated that naamine D, latrunculin A and S, (+)-curcudiol, (+)-curcuphenol, aurantoside I, and hyrtimomine A had the highest binding affinity values of −8.8, −8.6, −9.8, −11.4, −8.0, −11.4, and −9.0 kcal/mol, respectively. In sum, all MNPs included in this study are good candidates against mucormycosis. (+)-curcudiol and (+)-curcuphenol are promising compounds due to their broad-spectrum target inhibition potential.

Retinopathy of prematurity (ROP) is a largely avoidable cause of blindness in children worldwide, requiring high-quality neonatal care, early detection and treatment. In middle-income countries throughout Latin America, Eastern Europe and South Asia, there has been a rise in ROP blindness due to a combination of increased survival of preterm infants, resource-scarce medical environments and lack of policies, training and human resources. However, Argentina is an example of country where rates of ROP blindness have declined and ROP programmes have been successfully and effectively embedded within the health and legal system. The purpose of this study is to describe the activities and stakeholders, including Ministry of Health (MoH) and UNICEF, involved in the process, from recognition of an epidemic of ROP blindness to the development of national guidelines, policies and legislation for control. Using a retrospective mixed methods case study design, data on rates of severe ROP was collected from 13 neonatal intensive care units from 1999 to 2012, and on the proportion of children blind from ROP in nine blind schools in seven provinces. Legislative document review, focus group discussions and key informant interviews were conducted with neonatologists, ophthalmologists, neonatal nurses, parents, MoH officials, clinical societies, legislators and UNICEF officials in seven provinces. Results are presented combining the stages heuristic policy framework and Shiffman including: agenda setting, policy formulation, implementation and evaluation. By 2012, ROP had declined as a cause of blindness in children in schools for the blind as had rates of severe ROP needing treatment in the NICUs visited. Multiple factors played a role in reducing blindness from ROP in Argentina and successfully coordinating its control including national advocacy, leadership, legislation and international collaboration. Lessons learned in Argentina can potentially be scaled to other LMICs in Latin America and beyond with further context-specific research.

A 56-year-old female complained of diplopia immediately after surgical excision of a recurrent left skull base tuberculum meningioma. She was found to have a left sixth nerve palsy, which was subsequently treated with botulinum toxin injection to the medial rectus muscle. Three months post injection, the patient had partial recovery of the sixth nerve palsy and new-onset ocular neuromyotonia.

Background: Choroidal neovascularization (CNV) is a rare complication of intermediate uveitis. Risk factors are not well-characterized. Here, we describe a case of peripapillary CNV in a patient with intermediate uveitis and explore the pathophysiology and treatment of this condition. This study is a case report and review of the literature., Results: A 15-year-old boy with intermediate uveitis - suppressed for the preceding year on immunosuppressive therapy and low-dose corticosteroids - and chronic disc swelling presented with unilateral metamorphopsia, peripapillary subretinal hemorrhage, and subretinal fluid. Fluorescein angiogram confirmed the presence of an active choroidal neovascular membrane. Treatment with intravitreal bevacizumab 1.25 mg every 4 weeks for 4 months resulted in resolution of subretinal fluid, subretinal hemorrhage, and regression of the CNV. The patient's intermediate uveitis remained inactive throughout this time., Conclusion: Review of the existing literature and pathophysiologic consideration suggests that chronic disc edema may be a risk factor for this condition. Peripapillary CNV in the context of intermediate uveitis appears to respond well to VEGF-inhibitor therapy.

Introduction: Identifying communities with lower rates of mammography screening is a critical step to providing targeted screening programs; however, population-based data necessary for identifying these geographic areas are limited. This study presents methods to identify geographic disparities in the early detection of breast cancer., Methods: Data for all women residing in Dane County, Wisconsin, at the time of their breast cancer diagnosis from 1981 through 2000 (N = 4769) were obtained from the Wisconsin Cancer Reporting System (Wisconsin's tumor registry) by ZIP code of residence. Hierarchical logistic regression models for disease mapping were used to identify geographic differences in the early detection of breast cancer., Results: The percentage of breast cancer cases diagnosed in situ (excluding lobular carcinoma in situ) increased from 1.3% in 1981 to 11.9% in 2000. This increase, reflecting increasing mammography use, occurred sooner in Dane County than in Wisconsin as a whole. From 1981 through 1985, the proportion of breast cancer diagnosed in situ in Dane county was universally low (2%-3%). From 1986 through 1990, urban and suburban ZIP codes had significantly higher rates (10%) compared with rural ZIP codes (5%). From 1991 through 1995, mammography screening had increased in rural ZIP codes (7% of breast cancer diagnosed in situ). From 1996 through 2000, mammography use was fairly homogeneous across the entire county (13%-14% of breast cancer diagnosed in situ)., Conclusion: The percentage of breast cancer cases diagnosed in situ increased in the state and in all areas of Dane County from 1981 through 2000. Visual display of the geographic differences in the early detection of breast cancer demonstrates the diffusion of mammography use across the county over the 20-year period.