Interactive effects of age and respiratory virus on severe lower respiratory infection.

We investigated risk factors for severe acute lower respiratory infections (ALRI) among hospitalised children 8 months were at greater risk from influenza-associated ICU admissions and long hospital stay. Children with ADV had increased LOS across all ages. In the first 2 years of life, the effects of different viruses on ALRI severity varies with age. Our findings help to identify specific ages that would most benefit from virus-specific interventions such as vaccines and antivirals.

Density of day cares in relation to reported pertussis incidence in Philadelphia.

OBJECTIVES: Reported pertussis incidence has increased markedly in recent years. In addition to the documented increase in under-immunization and waning immunity, the increase may be related to the more frequent use of child care services by parents over the last few decades. Additionally, clustering of outbreaks may be related to neighborhood characteristics not previously identified. STUDY DESIGN: We conducted a citywide case-control study of children in Philadelphia aged birth through six years, between 2001 and 2013. Cases were reported as probable pertussis diagnoses to the Health Department. Controls were sampled from the city's immunization information system and matched to the cases by date of birth. METHODS: Multilevel logistic regression was used to isolate the independent contributions of individual and neighborhood risk factors and the corresponding relative odds of pertussis. The density of day cares in each neighborhood served as the main exposure and reported incident cases of confirmed and probable pertussis was the main outcome. RESULTS: Between 2001 and 2013, 410 cases of confirmed and probable pertussis were included with four controls matched per case yielding a final sample of 2050 children from 45 Philadelphia neighborhoods. There was a 30% increase in the risk of pertussis based solely on the neighborhood where the children resided (median odds ratio 1.3, 95% credible interval 1.1, 1.6). The density of day cares in each neighborhood was unrelated to the distribution of pertussis cases. CONCLUSIONS: Pertussis clustering was observed at the neighborhood level in Philadelphia, but was unrelated to the neighborhood's day care density. From a Health Department perspective, the highest risk neighborhoods should be targeted for vaccine campaigns and further research to identify the etiologic risk factors.

Evaluation of latent tuberculous infection and treatment completion for refugees in Philadelphia, PA, 2010-2012.

SETTING: Philadelphia, PA, USA. OBJECTIVES: To compare the evaluation and treatment of latent tuberculous infection (LTBI) in refugees seen at member clinics of the Philadelphia Refugee Health Collaborative (PRHC) vs. non-PRHC clinics. DESIGN: Refugees with Class B (non-communicable) tuberculosis (TB) admitted to the United States from 2010 to 2012 who were being treated at PRHC clinics were compared to those treated at non-PRHC clinics. Odds ratios (ORs) for attending a follow-up appointment, completing treatment, and time from arrival to the United States to the first TB screening test were calculated. RESULTS: Of the 2094 refugees who arrived in Philadelphia in 2010-2012, the Philadelphia Department of Public Health was notified of 149 who required additional evaluation for TB. Among these, 57 (38.3%) were confirmed to have LTBI, and none were diagnosed with active TB. All LTBI cases were recommended for anti-tuberculosis prophylaxis and 43 (75.4%) completed treatment. Refugees receiving care from PRHC clinics were more likely to be screened within 30 days of arrival (OR 4.70, 95%CI 2.12-10.44), attend a follow-up appointment (OR 4.53, 95%CI 1.36-16.27), and complete treatment (OR 9.44, 95%CI 2.39-37.3). CONCLUSION: Refugees who attended PRHC clinics were more likely to be evaluated promptly and to complete LTBI treatment. The PRHC clinics serve as a model for communities seeking to improve refugee health care.

Intragenic duplication and divergence in the spectrin superfamily of proteins.

Many structural, signaling, and adhesion molecules contain tandemly repeated amino acid motifs. The alpha-actinin/spectrin/dystrophin superfamily of F-actin-crosslinking proteins contains an array of triple alpha-helical motifs (spectrin repeats). We present here the complete sequence of the novel beta-spectrin isoform beta(Heavy)-spectrin (beta H). The sequence of beta H supports the origin of alpha- and beta-spectrins from a common ancestor, and we present a novel model for the origin of the spectrins from a homodimeric actin-crosslinking precursor. The pattern of similarity between the spectrin repeat units indicates that they have evolved by a series of nested, nonuniform duplications. Furthermore, the spectrins and dystrophins clearly have common ancestry, yet the repeat unit is of a different length in each family. Together, these observations suggest a dynamic period of increase in repeat number accompanied by homogenization within each array by concerted evolution. However, today, there is greater similarity of homologous repeats between species than there is across repeats within species, suggesting that concerted evolution ceased some time before the arthropod/vertebrate split. We propose a two-phase model for the evolution of the spectrin repeat arrays in which an initial phase of concerted evolution is subsequently retarded as each new protein becomes constrained to a specific length and the repeats diverge at the DNA level. This evolutionary model has general applicability to the origins of the many other proteins that have tandemly repeated motifs.

Molecular organization and alternative splicing in zipper, the gene that encodes the Drosophila non-muscle myosin II heavy chain.

Genomic sequence of the entire zipper gene, that encodes non-muscle myosin II heavy chain (MHC) in Drosophila melanogaster, reveals a new, differentially spliced exon in this essential locus and identifies a molecular lesion that is responsible for a severe embryonic lethal zipper allele. There are two alternative splices in the head domain. The first is present in the 5' untranslated sequence which, when employed, produces an N-terminal extension of 45 amino acids (aa). This splicoform produces a protein that is stable in flies but less prevalent than the isoform that lacks the extension. The second alternative exon (40 aa) is close to the nucleotide binding pocket. The position, size and sequence of this exon is conserved in D. simulans and putative alternative exons of different size (7 to 16 aa) but identical position have been reported for other myosins throughout phylogeny. The functional significance of neither alternative splice is clear. Sequence analysis of genomic DNA identifies the lesion responsible for zipIIF107, one of the original severe embryonic lethal zipper alleles. Our primary structural data confirm and correct our previous sequence of the cDNA, establish the spatial relationship between zipper and unzipped (the gene originally thought to have been disrupted in zipper mutations), and provide a high resolution template for the precise mapping of mutations.