To determine the safety, efficacy, and cost savings of early hospital discharge of very-low-birth-weight infants (less than or equal to 1500 g), we randomly assigned infants to one of two groups. Infants in the control group (n = 40) were discharged according to routine nursery criteria, which included a weight of about 2200 g. Those in the early-discharge group (n = 39) were discharged before they reached this weight if they met a standard set of conditions. For families of infants in the early-discharge group, instruction, counseling, home visits, and daily on-call availability of a hospital-based nurse specialist for 18 months were provided. Infants in the early-discharge group were discharged a mean of 11 days earlier, weighed 200 g less, and were two weeks younger at discharge than control infants. The mean hospital charge for the early-discharge group was 27 percent less than that for the control group ($47,520 vs. $64,940; P less than 0.01), and the mean physician's charge was 22 percent less ($5,933 vs. $7,649; P less than 0.01). The mean cost of the home follow-up care in the early-discharge group was $576, yielding a net saving of $18,560 for each infant. The two groups did not differ in the numbers of rehospitalizations and acute care visits, or in measures of physical and mental growth. We conclude that early discharge of very-low-birth-weight infants, with follow-up care in the home by a nurse specialist, is safe and cost effective.

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Cyclotides is a rapidly growing class of plant‐derived cyclic peptides exhibiting several bioactivities with potential applications in the agricultural and pharmaceutical sectors. Both natural and grafted cyclotides have shown promise in cancer therapy. Approximately 70 natural cyclotides belonging to three plant families (Fabaceae, Rubiaceae, and Violaceae) have shown cytotoxicity against several cancer cell lines. Cyclotides exhibit considerable stability against thermal and enzymatic proteolysis, owing to their unique structure with knotted topology and head to tail cyclization. Further, their small size, high stability, oral bioavailability, and tolerance to amino acid substitution in structural loops make them an ideal platform for designing peptide‐based drugs for cancer. Thus, cyclotides provide ideal scaffolds for bioactive epitope grafting and facilitating drug delivery in cancer treatment. Many anticancer linear peptides have been grafted in cysteine knotted cyclic framework of cyclotide for enhancing their cell permeability across cellular membranes, thereby improving their delivery and pharmacokinetics. The present review comprehensively discusses the distribution, toxicity, and anticancer bioactivity of natural cyclotides. Further, it systematically elaborates on the role and action of epitopes' into grafted cyclotides in targeting cancer. The review also encompasses related patents landscape study and future challenges in peptide‐based cancer therapy.

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Phosphorylation of the activation loop in the catalytic domain of the RD family of bacterial eukaryotic‐type Ser/Thr protein kinases (STPK) induces their conformational transition from an inactive to active state. However, mechanistic insights into the phosphorylation‐mediated transition of these STPKs from an inactive to active state remain unknown. In the present study, we addressed this issue with PknA, an essential STPK from Mycobacterium tuberculosis. We found that the catalytic activity of PknA is confined within the N‐terminal 283 amino acids (PknA‐283). The crystal structure of PknA‐283 in unphosphorylated form showed an ordered activation loop and existed in an inactive state preventing the phosphorylation of its cognate substrate(s). Peptide mass finger printing studies revealed that all activation loop threonines (Thr172, Thr174 and Thr180) were phosphorylated in the activated PknA‐283 protein. Substitution of Thr180 with Ala/Asp (T180A/T180D) resulted in catalytically defective mutants, whereas a double mutant replacing Thr172 and Thr174 with Ala (T172A‐T174A) was deficient in kinase activity. Analysis of PknA‐283 structure, together with biochemical studies, revealed the possibility of phosphorylation of Thr180 via a cis mechanism, whereas that of Thr172 and Thr174 occurs via a trans mechanism. Moreover, unlike wild‐type, these mutants did not show any drastic change in cell morphology in a phenotypic assay, implicating the role of all threonines in the activation loop towards the functionality of PknA. Thus, our findings offer a model for kinase activation showing that the phosphorylation of Thr180 triggers PknA to transphosphorylate Thr172/Thr174, thereby governing its functionality.