Increased microbial drug resistance has generated a global requirement for new anti-infective agents. As part of an effort to develop new, low-molecular-mass peptide antibiotics, we used a rationale-based minimalist approach to design short, nonhemolytic, potent, and broad-spectrum antibiotic peptides with increased serum stability. These peptides were designed to attain an amphipathic structure in helical conformations. VS1 was used as the lead compound, and its properties were compared with three series of derivates obtained by (i) N-terminal amino acid addition, (ii) systematic Trp substitution, and (iii) peptide dendrimerization. The Trp substitution approach underlined the optimized sequence of VS2 in terms of potency, faster membrane permeation, and cost-effectiveness. VS2 (a variant of VS1 with two Trp substitutions) was found to exhibit good antimicrobial activity against both the Gram-negative Escherichia coli and the Gram-positive bacterium Staphylococcus aureus. It was also found to have noncytolytic activity and the ability to permeate and depolarize the bacterial membrane. Lysis of the bacterial cell wall and inner membrane by the peptide was confirmed by transmission electron microscopy. A combination of small size, the presence of unnatural amino acids, high antimicrobial activity, insignificant hemolysis, and proteolytic resistance provides fundamental information for the de novo design of an antimicrobial peptide useful for the management of infectious disease.
Background:The technology enabled distributed model in Kerala is based on an innovative partnership model between Karkinos Healthcare and private health centers. The model is designed to address the barriers to cancer screening by generating demand and by bringing together the private health centers and service providers at various levels to create a network for continued care. This paper describes the implementation process and presents some preliminary findings. Methods: The model follows the hub-and-spoke and further spoke framework. In the pilot phases, from July 2021 to December 2021, five private health centers (partners) collaborated with Karkinos Healthcare across two districts in Kerala. Screening camps were organized across the districts at the community level where the target groups were administered a risk assessment questionnaire followed by screening tests at the spoke hospitals based on a defined clinical protocol. The screened positive patients were examined further for confirmatory diagnosis at the spoke centers. Patients requiring chemotherapy or minor surgeries were treated at the spokes. For radiation therapy and complex surgeries the patients were referred to the hubs. Results: A total of 2,459 individuals were screened for cancer at the spokes and 299 were screened positive. Capacity was built at the spokes for cancer surgery and chemotherapy. A total of 189 chemotherapy sessions and 17 surgeries were performed at the spokes for cancer patients. 70 patients were referred to the hub. Conclusion: Initial results demonstrate the ability of the technology Distributed Cancer Care Network (DCCN) system to successfully screen and detect cancer and to converge the actions of various private health facilities towards providing a continuum of cancer care. The lessons learnt from this study will be useful for replicating the process in other States.
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