Comparison of cumulative dispersed energy (CDE) in femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification.

PURPOSE: To compare the amount of phacoemulsification ultrasound energy used between eyes undergoing femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification. METHODS: One eye of consecutive patients undergoing routine non-complicated phacoemulsification from January 2014 to December of 2015 was included in the analysis. FLACS was performed using the Alcon LenSx. Linear regression was used for analysis with type of surgery (FLACS versus conventional phacoemulsification) as the exposure and cumulative dispersed energy (CDE) as the outcome variable. Age, surgeon, eye side, and eye sequence (first versus second eye) were covariates. RESULTS: A total of 1159 surgeries met inclusion criteria. The average age of the cohort was 70.6 (SD 8.6) years, 590 cases (51%) were performed by surgeon 1, and 582 cases (50%) were right eyes. Overall, FLACS resulted in significantly lower CDE as compared to conventional phacoemulsification (ß = 0.89, 95% CI 0.83, 0.95). When stratified by eye side and surgeon, FLACS performed on left eyes operated on by surgeon 1 resulted in lower CDE as compared to conventional phacoemulsification (ß = 0.76, 95% CI 0.66, 0.87), but not for right eyes operated on by surgeon 1 (ß = 0.92, 95% CI 0.79, 1.07) or for eyes operated on by surgeons 2 or 3. CONCLUSIONS: The use of FLACS on the Alcon LenSx platform results in a small decrease in phacoemulsification energy as compared to conventional phacoemulsification in certain cases. Further study assessing optimal laser settings and surgical technique is necessary.

Stillbirth gestational age as a predictor of recurrence risk.

OBJECTIVE: We evaluated risk of subsequent stillbirth (SB) according to gestational age at initial SB. STUDY DESIGN: We retrospectively reviewed a cohort of women delivering a singleton SB with at least one subsequent pregnancy. Relative risks (RRs) were calculated using an initial SB gestational age of 36 to < 40 weeks as the referent. Multivariable logistic regression accounted for potential confounders. RESULTS: In all, 2,887 mothers and 5,090 subsequent births met inclusion criteria. For the immediately next pregnancy, the linear trend for gestational age was not significant (RR 0.41; 95% confidence interval [CI] 0.03 to 5.53). However, women with index SBs occurring between 20 and 23(6/7) weeks' gestation had a RR for subsequent stillbirth of 2.9 (95% CI 1.2 to 7.1). When including subsequent pregnancies, the test for trend for gestational age was nonsignificant (RR 1.5; 95% CI 0.3 to 8.7). However, women suffering a stillbirth between 20(0/7) and 23(6/7) weeks' gestation in the index pregnancy had an almost threefold increase in the risk of subsequent stillbirth. Women suffering an index stillbirth between 28(0/7) and 31(6/7) weeks' and after 40 weeks' gestation had a 2.5- to 3.5-fold increased risk of subsequent SB. CONCLUSIONS: Gestational age at initial SB predicts risk of recurrent SB. This effect is most pronounced in women with very preterm or with postterm pregnancies.

Identifying clinical/translational research cohorts: ascertainment via querying an integrated multi-source database.

BACKGROUND: Ascertainment of potential subjects has been a longstanding problem in clinical research. Various methods have been proposed, including using data in electronic health records. However, these methods typically suffer from scaling effects-some methods work well for large cohorts; others work for small cohorts only. OBJECTIVE: We propose a method that provides a simple identification of pre-research cohorts and relies on data available in most states in the USA: merged public health data sources. MATERIALS AND METHODS: The Utah Population Database Limited query tool allows users to build complex queries that may span several types of health records, such as cancer registries, inpatient hospital discharges, and death certificates; in addition, these can be combined with family history information. The architectural approach incorporates several coding systems for medical information. It provides a front-end graphical user interface and enables researchers to build and run queries and view aggregate results. Multiple strategies have been incorporated to maintain confidentiality. RESULTS: This tool was rapidly adopted; since its release, 241 users representing a wide range of disciplines from 17 institutions have signed the user agreement and used the query tool. Three examples are discussed: pregnancy complications co-occurring with cardiovascular disease; spondyloarthritis; and breast cancer. DISCUSSION AND CONCLUSIONS: This query tool was designed to provide results as pre-research so that institutional review board approval would not be required. This architecture uses well-described technologies that should be within the reach of most institutions.

A functional -1 ribosomal frameshift signal in the human paraneoplastic Ma3 gene.

A bioinformatics approach to finding new cases of -1 frameshifting in the expression of human genes revealed a classical retrovirus-like heptanucleotide shift site followed by a potential structural stimulator in the paraneoplastic antigen Ma3 and Ma5 genes. Analysis of the sequence 3' of the shift site demonstrated that an RNA pseudoknot in Ma3 is important for promoting efficient -1 frame-shifting. Ma3 is a member of a family of six genes in humans whose protein products contain homology to retroviral Gag proteins. The -1 frameshift site and pseudoknot structure are conserved in other mammals, but there are some sequence differences. Although the functions of the Ma genes are unknown, the serious neurological effects of ectopic expression in tumor cells indicate their importance in the brain.

Transcriptional slippage in bacteria: distribution in sequenced genomes and utilization in IS element gene expression.

BACKGROUND: Transcription slippage occurs on certain patterns of repeat mononucleotides, resulting in synthesis of a heterogeneous population of mRNAs. Individual mRNA molecules within this population differ in the number of nucleotides they contain that are not specified by the template. When transcriptional slippage occurs in a coding sequence, translation of the resulting mRNAs yields more than one protein product. Except where the products of the resulting mRNAs have distinct functions, transcription slippage occurring in a coding region is expected to be disadvantageous. This probably leads to selection against most slippage-prone sequences in coding regions. RESULTS: To find a length at which such selection is evident, we analyzed the distribution of repetitive runs of A and T of different lengths in 108 bacterial genomes. This length varies significantly among different bacteria, but in a large proportion of available genomes corresponds to nine nucleotides. Comparative sequence analysis of these genomes was used to identify occurrences of 9A and 9T transcriptional slippage-prone sequences used for gene expression. CONCLUSIONS: IS element genes are the largest group found to exploit this phenomenon. A number of genes with disrupted open reading frames (ORFs) have slippage-prone sequences at which transcriptional slippage would result in uninterrupted ORF restoration at the mRNA level. The ability of such genes to encode functional full-length protein products brings into question their annotation as pseudogenes and in these cases is pertinent to the significance of the term 'authentic frameshift' frequently assigned to such genes.

Sequences that direct significant levels of frameshifting are frequent in coding regions of Escherichia coli.

It is generally believed that significant ribosomal frameshifting during translation does not occur without a functional purpose. The distribution of two frameshift-prone sequences, A_AAA_AAG and CCC_TGA, in coding regions of Escherichia coli has been analyzed. Although a moderate level of selection against the first sequence is evident, 68 genes contain A_AAA_AAG and 19 contain CCC_TGA. The majority of those tested in their genomic context showed >1% frameshifting. Comparative sequence analysis was employed to assess a potential biological role for frameshifting in decoding these genes. Two new candidates, in pheL and ydaY, for utilized frameshifting have been identified in addition to those previously known in dnaX and nine insertion sequence elements. For the majority of the shift-prone sequences no functional role can be attributed to them, and the frameshifting is likely erroneous. However, none of frameshift sequences is in the 306 most highly expressed genes. The unexpected conclusion is that moderate frameshifting during expression of at least some other genes is not sufficiently harmful for cells to trigger strong negative evolutionary pressure.

RECODE 2003.

The RECODE database is a compilation of translational recoding events (programmed ribosomal frameshifting, codon redefinition and translational bypass). The database provides information about the genes utilizing these events for their expression, recoding sites, stimulatory sequences and other relevant information. The Database is freely available at http://recode.genetics.utah.edu/.