Murine obscurin and Obsl1 have functionally redundant roles in sarcolemmal integrity, sarcoplasmic reticulum organization, and muscle metabolism.

Biological roles of obscurin and its close homolog Obsl1 (obscurin-like 1) have been enigmatic. While obscurin is highly expressed in striated muscles, Obsl1 is found ubiquitously. Accordingly, obscurin mutations have been linked to myopathies, whereas mutations in Obsl1 result in 3M-growth syndrome. To further study unique and redundant functions of these closely related proteins, we generated and characterized Obsl1 knockouts. Global Obsl1 knockouts are embryonically lethal. In contrast, skeletal muscle-specific Obsl1 knockouts show a benign phenotype similar to obscurin knockouts. Only deletion of both proteins and removal of their functional redundancy revealed their roles for sarcolemmal stability and sarcoplasmic reticulum organization. To gain unbiased insights into changes to the muscle proteome, we analyzed tibialis anterior and soleus muscles by mass spectrometry, uncovering additional changes to the muscle metabolism. Our analyses suggest that all obscurin protein family members play functions for muscle membrane systems

Molecular epidemiology of human rhinovirus infections in Kilifi, coastal Kenya

This study reports pediatric surveillance over 3 years for human rhinovirus (HRV) at the District Hospital of Kilifi, coastal Kenya. Nasopharyngeal samples were collected from children presenting at outpatient clinic with no signs of acute respiratory infection, or with signs of upper respiratory tract infection, and from children admitted to the hospital with lower respiratory tract infection. Samples were screened by real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) and classified further to species by nucleotide sequencing of the VP4/VP2 junction. Of 441 HRV positives by real-time RT-PCR, 332 were classified to species, with 47% (155) being HRV-A, 5% (18) HRV-B, and 48% (159) HRV-C. There was no clear seasonal pattern of occurrence for any species. The species were present in similar proportions in the inpatient and outpatient sample sets, and no significant association between species distribution and the severity of lower respiratory tract infection in the inpatients could be determined. HRV sequence analysis revealed multiple but separate clusters in circulation particularly for HRV-A and HRV-C. Most HRV-C clusters were distinct from reference sequences downloaded from GenBank. In contrast, most HRV-A and HRV-B sequences clustered with either known serotypes or strains from elsewhere within Africa and other regions of the world. This first molecular epidemiological study of HRV in the region defines species distribution in accord with reports from elsewhere in the world, shows considerable strain diversity and does not identify an association between any species and disease severity

Surfactant use based on the oxygenation response to lung recruitment during HFOV in VLBW infants

Purpose: Early lung recruitment (ELR) during high-frequency oscillatory ventilation (HFOV) in combination with prophylactic surfactant use has been reported to reduce mortality, improve respiratory outcomes, and reduce the need for repeated surfactant dosing, suggesting that surfactant might be used more selectively in very low birth weight (VLBW) infants on HFOV than generally recommended. We report our first experience from such a selective early rescue use of surfactant in VLBW infants on HFOV. Methods: After a deliberate ELR maneuver and "optimal” continuous distending pressure (CDP) finding during HFOV, used as primary ventilation mode for VLBW infants with respiratory distress syndrome (RDS), surfactant was only given when an unsatisfactory oxygenation response to lung recruitment (as defined by CDP×FiO2>5) was observed. Results: Out of 144 VLBW infants on HFOV, 84 (58.3%) received surfactant and 60 (41.7%) did not. Duration of required oxygen supplementation (37.4±44.9 vs. 46.2±35.4days; P=0.031) and respiratory support (i.e., n-CPAP and/or mechanical ventilation; 22.3±19.3 vs. 38.2±24.3days; P=0.001) was shorter for infants who did not receive surfactant than for those who did. The incidence and severity of bronchopulmonary dysplasia was similar in both groups, and there was no difference in survival rates between groups. Subgroup analysis for infants of less than 28weeks of gestation revealed similar results. Conclusions: First intention HFOV combined with an early attempt at lung volume optimization might allow surfactants to be used more selectively (in relation to disease severity) in VLBW infants presenting with RDS at birth without negatively influencing the outcom