Drug-resistant Streptococcus pneumoniae

To the Editor: since the first description of infection caused by β-lactam-resistant Streptococcus pneumoniae, the optimal empirical antibiotic therapy for patients with suspected meningitis caused by this microorganism has remained unknown. Hofmann et al. (Aug. 24 issue)1 reported a 25 percent prevalence of penicillin-resistant S. pneumoniae isolates and a 9 percent prevalence of cephalosporin-resistant isolates among 431 patients with invasive pneumococcal infections in Atlanta. The authors recommended adding vancomycin to the initial therapeutic regimen of patients with suspected pneumococcal meningitis

Estimating the cumulative effects of the nature-based tourism in a coastal dolphin population from southern Kenya

Due to the growth of nature-based tourism worldwide, behavioural studies are needed to assess the impact of this industry on wildlife populations and understand their short-term effect. Tourism impact on dolphin populations remain poorly documented in developing countries. This study investigates the effects of nature-based tourism on the behaviour of the Indo-Pacific bottlenose dolphins (Tursiops aduncus) in southern Kenya. We used Markov chain models to estimate transition probabilities between behavioural states in the presence and absence of tourist boats, and assess the overall behavioural budgets. Based on these data and the tourism intensity in the area, we quantified the potential tourist boat disturbance over the period 2006-2013. Our results demonstrated that tourist boat interactions affected dolphins' behavioural budgets, with a significant decrease in the overall amount of time travelling and an increase in diving. The average duration of travelling and resting decreased significantly in the presence of boats. Although the cumulative tourism exposure was not significant for the dolphin population at their current levels, these impacts should be taken into consideration with the potential tourism growth in the area. This is particularly important if tourism reaches periods of high intensity, as we have shown that these periods could have a significant impact for the species, particularly where home-range and core areas are highly overlap by this activity. Understanding the effect of human disturbance variations from previous years may help to predict the consequences on dolphin populations, towards achieving a more ecological and economic sustainability of the activity

ATG5 overexpression is neuroprotective and attenuates cytoskeletal and vesicle-trafficking alterations in axotomized motoneurons

Injured neurons should engage endogenous mechanisms of self-protection to limit neurodegeneration. Enhancing efficacy of these mechanisms or correcting dysfunctional pathways may be a successful strategy for inducing neuroprotection. Spinal motoneurons retrogradely degenerate after proximal axotomy due to mechanical detachment (avulsion) of the nerve roots, and this limits recovery of nervous system function in patients after this type of trauma. In a previously reported proteomic analysis, we demonstrated that autophagy is a key endogenous mechanism that may allow motoneuron survival and regeneration after distal axotomy and suture of the nerve. Herein, we show that autophagy flux is dysfunctional or blocked in degenerated motoneurons after root avulsion. We also found that there were abnormalities in anterograde/retrograde motor proteins, key secretory pathway factors, and lysosome function. Further, LAMP1 protein was missorted and underglycosylated as well as the proton pump v-ATPase. In vitro modeling revealed how sequential disruptions in these systems likely lead to neurodegeneration. In vivo, we observed that cytoskeletal alterations, induced by a single injection of nocodazole, were sufficient to promote neurodegeneration of avulsed motoneurons. Besides, only pre-treatment with rapamycin, but not post-treatment, neuroprotected after nerve root avulsion. In agreement, overexpressing ATG5 in injured motoneurons led to neuroprotection and attenuation of cytoskeletal and trafficking-related abnormalities. These discoveries serve as proof of concept for autophagy-target therapy to halting the progression of neurodegenerative processes

Essential ocean variables and high value biodiversity areas: Targets for the conservation of marine megafauna

Effective conservation and management measures are needed to face the unprecedented changes that marine ecosystems, and particularly marine megafauna, are suffering. These measures require the identification of highvalue biodiversity areas (HVBAs) which in turn require the identification of the essential ocean variables (EOVs) that shape the environmental envelope of communities (i.e. space defined by a set of environmental variables). The aim of this study was to delineate and characterise the HVBAs for the north and northwestern Spanish seabird and cetacean community taking advantage of the sightings collected during the annual PELACUS oceanographic survey (2007–2016). We used distance sampling methodology to analyse the species detectability based on environmental conditions. Then, we delimitated the HVBAs and identified the EOVs defining the environmental envelope of the community based on a spatio-temporal modelling approach using Generalized Additive Models. Overall, the main environmental variables driving species abundance were the sea surface temperature (SST), the distance to the shelf-break and the chlorophyll-a concentration (Chl-a). The SST and Chla were identified as dynamic EOVs due to their highest relative predictor importance, driving the environmental envelope and shaping areas of higher density. HVBAs were located mainly over the northwestern Spanish waters and decreased towards the inner Bay of Biscay remaining spatially stable over the study period. By identifying community-level HVBAs, we can understand the underlying ecological and oceanographic processes driving the spatio-temporal patterns of biological communities, such as those composed by seabirds and cetaceans. This information would identify conservation targets to assist the allocation of management resources. In addition, the location of HVBAs can help to fulfil the emergent need for sound spatial information to support the implementation of marine spatial planning.En prens

Bacterial lysis through interference with peptidoglycan synthesis increases biofilm formation by nontypeable haemophilus influenzae

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that mainly causes otitis media in children and community-acquired pneumonia or exacerbations of chronic obstructive pulmonary disease in adults. A large variety of studies suggest that biofilm formation by NTHi may be an important step in the pathogenesis of this bacterium. However, the underlying mechanisms involved in this process are poorly elucidated. In this study, we used a transposon mutant library to identify bacterial genes involved in biofilm formation. The growth and biofilm formation of 4,172 transposon mutants were determined, and the involvement of the identified genes in biofilm formation was validated in in vitro experiments. Here, we present experimental data showing that increased bacterial lysis, through interference with peptidoglycan synthesis, results in elevated levels of extracellular DNA, which increased biofilm formation. Interestingly, similar results were obtained with subinhibitory concentrations of β-lactam antibiotics, known to interfere with peptidoglycan synthesis, but such an effect does not appear with other classes of antibiotics. These results indicate that treatment with β-lactam antibiotics, especially for β-lactam-resistant NTHi isolates, might increase resistance to antibiotics by increasing biofilm formation

Specific IgA against Pseudomonas aeruginosa in severe COPD

Background: The bronchial mucosa is protected by a specialized immune system focused on the prevention of colonization and infection by potentially pathogenic microorganisms (PPMs). Immunoglobulin A (IgA) is the principal antibody involved in this mechanism. A defective immune barrier may facilitate the recurrent presence of PPMs in COPD. Purpose: The aim of this study was to determine IgA-mediated bronchial specific immune responses against Pseudomonas aeruginosa in stable patients with severe disease. Methods: COPD patients with good-quality sputum samples obtained during stability were included and classified according to the presence or absence of chronic bronchial colonization by P. aeruginosa. Levels of specific IgA for P. aeruginosa in sputum were determined by ELISA and expressed as ratios, using the pooled level of 10 healthy subjects as reference (optical density450 patient/control). Results: Thirty-six stable COPD patients were included, 15 of whom had chronic colonization by P. aeruginosa. Levels of specific IgA against P. aeruginosa in stable non-colonized patients were lower than those in healthy subjects (IgA ratio: median =0.15 [interquartile range {IQR} 0.05-0.36]). Colonized patients had higher levels, (1.56 [IQR 0.59-2.79]) (p,0.001, Mann- Whitney U test), with figures equivalent but not exceeding the reference value. Conclusion: IgA-based immune response against P. aeruginosa was low in severe COPD patients. Levels of specific IgA against this microorganism were higher in colonized patients, but did not attain clear-cut levels above the reference. An impaired local response against P. aeruginosa may favor chronic colonization and recurrent infections in severe COPD

Endothelial loss of Fzd5 stimulates PKC/Ets1-mediated transcription of Angpt2 and Flt1

Aims: Formation of a functional vascular system is essential and its formation is a highly regulated process initiated during embryogenesis, which continues to play important roles throughout life in both health and disease. In previous studies, Fzd5 was shown to be critically involved in this process and here we investigated the molecular mechanism by which endothelial loss of this receptor attenuates angiogenesis. Methods and results: Using short interference RNA-mediated loss-of-function assays, the function and mechanism of signaling via Fzd5 was studied in human endothelial cells (ECs). Our findings indicate that Fzd5 signaling promotes neovessel formation in vitro in a collagen matrix-based 3D co-culture of primary vascular cells. Silencing of Fzd5 reduced EC proliferation, as a result of G0/G1 cell cycle arrest, and decreased cell migration. Furthermore, Fzd5 knockdown resulted in enhanced expression of the factors Angpt2 and Flt1, which are mainly known for their destabilizing effects on the vasculature. In Fzd5-silenced ECs, Angpt2 and Flt1 upregulation was induced by enhanced PKC signaling, without the involvement of canonical Wnt signaling, non-canonical Wnt/Ca2+-mediated activation of NFAT, and non-canonical Wnt/PCP-mediated activation of JNK. We demonstrated that PKC-induced transcription of Angpt2 and Flt1 involved the transcription factor Ets1. Conclusions: The current study demonstrates a pro-angiogenic role of Fzd5, which was shown to be involved in endothelial tubule formation, cell cycle progression and migration, and partly does so by repression of PKC/Ets1-mediated transcription of Flt1 and Angpt2