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Antimicrobial peptides (AMPs) have gained the attention of the research community for being an alternative to conventional antimicrobials to fight antibiotic resistance and for displaying other pharmacologically relevant activities, such as cell penetration, autophagy induction, immunomodulation, among others. The identification of AMPs had been accomplished by combining computational and experimental approaches and have been mostly restricted to self-contained peptides despite accumulated evidence indicating AMPs may be found embedded within proteins, the functions of which are not necessarily associated with antimicrobials. To address this limitation, we propose a machine-learning (ML)-based pipeline to identify AMPs that are embedded in proteomes. Our method performs an in-silico digestion of every protein in the proteome to generate unique k-mers of different lengths, computes a set of molecular descriptors for each k-mer, and performs an antimicrobial activity prediction. To show the efficiency of the method we used the shrimp proteome, and the pipeline analyzed all k-mers between 10 and 60 amino acids in length to predict all AMPs in less than 20 min. As an application example we predicted AMPs in different rodents (common cuy, common rat, and naked mole rat) with different reported longevities and found a relation between species longevity and the number of predicted AMPs. The analysis shows as the longevity of the species is higher, the number of predicted AMPs is also higher. The pipeline is available as a web service.
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Introduction The purpose of this study is to perform a cross-cultural adaptation and validation of the translated Patient-Rated Wrist Evaluation (PRWE) score exclusively for pathologies of the wrist. Materials and Methods A methodological study of cross-cultural validation of clinical scores was performed through a test-retest reliability analysis, internal consistency, response to change, and criterion validity assessment. Results The test was applied to 57 patients with 139 surveys. Stability evaluated through Lin's concordance correlation coefficient was 0.98, with 95% confidence interval (CI) = 0.97-0.99; Cronbach's alpha was > 0.91; the difference in score was 24.26 (standard deviation: 26.59); the standardized response mean was 0.912; the effect size was 0.924; the Spearman's coefficient between the differences of PRWE and DASH-Disabilities of the Arm, Shoulder, and Hand-scores was r = 0.899, with 95% CI = 0.811-0.947; Spearman's nonparametric correlation test between PRWE and DASH was 0.82, with 95% CI = 0.711-0.890. Conclusions We successfully validated the Spanish translation of the PRWE scale. It showed valid and reliable interpretation of functional status and response to treatment after distal radius fracture, for Colombian population. Level of Evidence This is a level II, methodological study for scale validation.
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Coxsackievirus A24 variant (CVA24v), the main causative agent of acute hemorrhagic conjunctivitis (AHC), can be isolated from both the eyes and lower alimentary tract. However, the molecular features of CVA24v in feces is not well-documented. In this study, we compared the VP1 and 3C sequences of CVA24v strains isolated from feces during AHC epidemics in Cuba in 1997, 2003, and 2008-2009 with those obtained from conjunctival swabs during the same epidemic period. The sequence analyses of the 3C and VP1 region of stool isolates from the three epidemics showed a high degree of nucleotide identity (ranging from 97.3-100%) to the corresponding conjunctival isolates. The phylogenetic analysis showed that fecal CVA24v isolates from the 1997 and 2003 Cuban outbreaks formed a clade with CVA24v strains isolated from conjunctival swabs in Cuba and other countries during the same period. There were three amino acid changes (3C region) and one amino acid change (VP1 region) in seven CVA24v strains isolated sequentially over 20 days from fecal samples of one patient, suggesting viral replication in the intestine. Despite these substitutions, the virus from the conjunctival swab and fecal samples were genetically very similar. Therefore, fecal samples should be considered as a reliable alternative sample type for the routine molecular diagnosis and molecular epidemiology of CVA24v, also during outbreaks of AHC.
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Coxsackievirus A24 variant (CVA24v) is a major causative agent of acute hemorrhagic conjunctivitis outbreaks worldwide, yet the evolutionary and transmission dynamics of the virus remain unclear. To address this, we analyzed and compared the 3C and partial VP1 gene regions of CVA24v isolates obtained from five outbreaks in Cuba between 1986 and 2009 and strains isolated worldwide. Here we show that Cuban strains were homologous to those isolated in Africa, the Americas and Asia during the same time period. Two genotypes of CVA24v (GIII and GIV) were repeatedly introduced into Cuba and they arose about two years before the epidemic was detected. The two genotypes co-evolved with a population size that is stable over time. However, nucleotide substitution rates peaked during pandemics with 4.39 × 10-3 and 5.80 × 10-3 substitutions per site per year for the 3C and VP1 region, respectively. The phylogeographic analysis identified 25 and 19 viral transmission routes based on 3C and VP1 regions, respectively. Pandemic viruses usually originated in Asia, and both China and Brazil were the major hub for the global dispersal of the virus. Together, these data provide novel insight into the epidemiological dynamics of this virus and possibly other pandemic viruses.