Shorter courses of parenteral antibiotic therapy do not appear to influence response rates for children with acute hematogenous osteomyelitis: a systematic review

BACKGROUND: Acute hematogenous osteomyelitis (AHO) occurs primarily in children and is believed to evolve from bacteremia followed by localization of infection to the metaphysis of bones. Currently, there is no consensus on the route and duration of antimicrobial therapy to treat AHO. METHODS: We conducted a systematic review of a short versus long course of treatment for AHO due primarily to Staphylococcus aureus in children aged 3 months to 16 years. We searched Medline, Embase and the Cochrane trials registry for controlled trials. Clinical cure rate at 6 months was the primary outcome variable, and groups receiving less than 7 days of intravenous therapy were compared with groups receiving one week or longer of intravenous antimicrobials. RESULTS: 12 eligible prospective studies, one of which was randomized, were identified. The overall cure rate at 6 months for the short course of intravenous therapy was 95.2% (95% CI = 90.4, 97.7) compared to 98.8% (95% CI = 93.6, 99.8) for the longer course of therapy. There was no significant difference in the duration of oral therapy between the two groups. CONCLUSIONS: Given the potential increased morbidity and cost associated with longer courses of intravenous therapy, this finding should be confirmed through a randomized controlled equivalence trial

Evidence that Adaptation in Drosophila Is Not Limited by Mutation at Single Sites

Adaptation in eukaryotes is generally assumed to be mutation-limited because of small effective population sizes. This view is difficult to reconcile, however, with the observation that adaptation to anthropogenic changes, such as the introduction of pesticides, can occur very rapidly. Here we investigate adaptation at a key insecticide resistance locus (Ace) in Drosophila melanogaster and show that multiple simple and complex resistance alleles evolved quickly and repeatedly within individual populations. Our results imply that the current effective population size of modern D. melanogaster populations is likely to be substantially larger (≥100-fold) than commonly believed. This discrepancy arises because estimates of the effective population size are generally derived from levels of standing variation and thus reveal long-term population dynamics dominated by sharp—even if infrequent—bottlenecks. The short-term effective population sizes relevant for strong adaptation, on the other hand, might be much closer to census population sizes. Adaptation in Drosophila may therefore not be limited by waiting for mutations at single sites, and complex adaptive alleles can be generated quickly without fixation of intermediate states. Adaptive events should also commonly involve the simultaneous rise in frequency of independently generated adaptive mutations. These so-called soft sweeps have very distinct effects on the linked neutral polymorphisms compared to the standard hard sweeps in mutation-limited scenarios. Methods for the mapping of adaptive mutations or association mapping of evolutionarily relevant mutations may thus need to be reconsidered

Maladaptive Habitat Selection of a Migratory Passerine Bird in a Human-Modified Landscape

In human-altered environments, organisms may preferentially settle in poor-quality habitats where fitness returns are lower relative to available higher-quality habitats. Such ecological trapping is due to a mismatch between the cues used during habitat selection and the habitat quality. Maladaptive settlement decisions may occur when organisms are time-constrained and have to rapidly evaluate habitat quality based on incomplete knowledge of the resources and conditions that will be available later in the season. During a three-year study, we examined settlement decision-making in the long-distance migratory, open-habitat bird, the Red-backed shrike (Lanius collurio), as a response to recent land-use changes. In Northwest Europe, the shrikes typically breed in open areas under a management regime of extensive farming. In recent decades, Spruce forests have been increasingly managed with large-size cutblocks in even-aged plantations, thereby producing early-successional vegetation areas that are also colonised by the species. Farmland and open areas in forests create mosaics of two different types of habitats that are now occupied by the shrikes. We examined redundant measures of habitat preference (order of settlement after migration and distribution of dominant individuals) and several reproductive performance parameters in both habitat types to investigate whether habitat preference is in line with habitat quality. Territorial males exhibited a clear preference for the recently created open areas in forests with higher-quality males settling in this habitat type earlier. Reproductive performance was, however, higher in farmland, with higher nest success, offspring quantity, and quality compared to open areas in forests. The results showed strong among-year consistency and we can therefore exclude a transient situation. This study demonstrates a case of maladaptive habitat selection in a farmland bird expanding its breeding range to human-created open habitats in plantations. We discuss the reasons that could explain this decision-making and the possible consequences for the population dynamics and persistence

Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory

The role of Drosophila Piezo in mechanical nociception

Transduction of mechanical stimuli by receptor neurons is essential for senses such as hearing, touch, and pain(1–4). Ion channels play a role in neuronal mechanotransduction in invertebrates(1); however, functional conservation of these ion channels in mammalian mechanotransduction is not observed. For example, NOMPC, a TRP ion channel, acts as a mechanotransducer in Drosophila melanogaster(5) and Caenorhabditis elegans(6,7); however, it has no orthologues in mammals. DEG/ENaC family members are mechanotransducers in C. elegans(8) and potentially in D. melanogaster(9); however, a direct role of its mammalian homologues in sensing mechanical force is not shown. Recently, Piezo1 and Piezo2 were identified as components of mechanically activated (MA) channels in mammals(10). Piezos represent an evolutionary conserved family of transmembrane proteins. It is unknown whether Piezos function in mechanical sensing in vivo, and if they do, which mechanosensory modalities they mediate. Here, we study the physiological role of the single Piezo member in D. melanogaster (dpiezo). dpiezo expression in human cells induces mechanically activated currents, similar to its mammalian counterparts [Coste et al., accompanying paper(11)]. Behavioral responses to noxious mechanical stimuli were severely reduced in dpiezo knockout larvae, while responses to another noxious stimulus or touch were not affected. Knocking down dpiezo in sensory neurons that mediate nociception and express the DEG/ENaC ion channel pickpocket (ppk) was sufficient to impair responses to noxious mechanical stimuli. Furthermore, expression of dpiezo in these same neurons rescued the phenotype of the constitutive dpiezo knockout larvae. Accordingly, electrophysiological recordings from ppk-positive neurons revealed a dpiezo dependent, mechanically-activated current. Finally, we found that dpiezo and ppk function in parallel pathways in ppk-positive cells, and that mechanical nociception is abolished in the absence of both channels. These data demonstrate physiological relevance of Piezo family in mechanotransduction in vivo, supporting a role of Piezo proteins in mechanosensory nociception