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Bloodstream infections (BSIs) and subsequent organ dysfunction (sepsis and septic shock) are conditions that rank among the top reasons for human mortality and have a great impact on healthcare systems. Their treatment mainly relies on the administration of broad-spectrum antimicrobials since the standard blood culture-based diagnostic methods remain time-consuming for the pathogen's identification. Consequently, the routine use of these antibiotics may lead to downstream antimicrobial resistance and failure in treatment outcomes. Recently, significant advances have been made in improving several methodologies for the identification of pathogens directly in whole blood especially regarding specificity and time to detection. Nevertheless, for the widespread implementation of these novel methods in healthcare facilities, further improvements are still needed concerning the sensitivity and cost-effectiveness to allow a faster and more appropriate antimicrobial therapy. This review is focused on the problem of BSIs and sepsis addressing several aspects like their origin, challenges, and causative agents. Also, it highlights current and emerging diagnostics technologies, discussing their strengths and weaknesses., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

Biological invasions of vectorborne diseases can be devastating. Bioclimatic modeling provides an opportunity to assess and predict areas at risk from complex multitrophic interactions of pathogens, highlighting areas in need of increased monitoring effort. Here, we model the distribution of an economically critical vectorborne plant pathogen 'Candidatus Phytoplasma aurantifolia', the etiological agent of Witches' Broom Disease of Lime. This disease is a significant limiting factor on acid lime production (Citrus aurantifolia, Swingle) in the Middle East and threatens its production globally. We found that temperature, humidity, and the vector populations significantly determine disease distribution. Following this, we used bioclimatic modeling to predict potential novel sites of infections. The model outputs identified potential novel sites of infection in the citrus producing regions of Brazil and China. We also used our model to explore sites in Oman where the pathogen may not be infectious, and suggest nurseries be established there. Recent major turbulence in the citrus agricultural economy has highlighted the importance of this work and the need for appropriate and targeted monitoring programs to safeguard lime production.

Background: Atypical bacteria are treatable causative agents of community-acquired pneumonia (CAP). However, there is no conclusive evidence that a child with CAP should receive empirical treatment against such agents., Objectives: We assessed the possibility of association between clinical failure and acute infection by these bacteria among children with CAP treated with amoxicillin., Patients and Methods: Patients aged 2-59 months with non-severe CAP received amoxicillin during prospective follow-up. Acute and convalescent blood samples were collected. Probable acute infection by Mycoplasma pneumoniae (specific IgM antibodies), by Chlamydia pneumoniae or Chlamydia trachomatis (specific IgM antibodies and/or IgG/IgA titre change) was investigated. Outcomes were assessed during follow-up at 2, 5 and 14-28 days. Treatment failure included development of danger signs, persistent fever, tachypnoea or death. ClinicalTrials.gov: NCT01200706., Results: Of 787 children, 86 (10.9%; 95% CI = 8.9%-13.3%) had acute M. pneumoniae infection. C. pneumoniae acute infection was found in 79 of 733 (10.8%; 95% CI = 8.7%-13.2%) and C. trachomatis was found in 3 of 28 (10.7%; 95% CI = 2.8%-26.5%) <6 months old. Among patients with or without treatment failure at 2 days, acute M. pneumoniae infection (11.7% versus 10.7%; P  =   0.7), acute C. pneumoniae infection (8.5% versus 11.3%; P  =   0.3) and acute C. trachomatis infection (16.7% versus 9.1%; P  =   0.5) were found. No significant differences were found with regard to treatment failure at the 5 day evaluation. Overall, amoxicillin was substituted in 3.5% versus 2.7% among patients with or without acute infection by one of these bacteria ( P  =   0.6)., Conclusions: The overall substitution rate of amoxicillin was very low. It is not necessary to give an empirical non-β-lactam antibiotic as a first-line option to treat every child between 2 and 59 months old with non-severe CAP., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The aim of this study was describe national trends in prevalence, demographics, hospital length of stay (LOS), hospital charges, and mortality for burn patients with and without inhalational injury and to compare to the National Burn Repository. Burns and inhalation injury cause considerable mortality and morbidity in the United States. There remains insufficient reporting of the demographics and outcomes surrounding such injuries. The National Inpatient Sample database, the nation's largest all-payer inpatient care data repository, was utilized to select 506,628 admissions for burns from 1988 to 2008 based on ICD-9-CM recording. The data were stratified based on the extent of injury (%TBSA) and presence or absence of inhalational injury. Inhalation injury was observed in only 2.2% of burns with <20% TBSA but 14% of burns with 80 to 99% TBSA. Burn patients with inhalation injury were more likely to expire in-hospital compared to those without (odds ratio, 3.6; 95% confidence interval, 2.7-5.0; P < .001). Other factors associated with higher mortality were African-American race, female sex, and urban practice setting. Patients treated at rural facilities and patients with hyperglycemia had lower mortality rates. Each increase in percent of TBSA of burns increased LOS by 2.5%. Patients with burns covering 50 to 59% of TBSA had the longest hospital stay at a median of 24 days (range, 17-55). The median in-hospital charge for a burn patient with inhalation injury was US$32,070, compared to US$17,600 for those without. Overall, patients who expired from burn injury accrued higher in-hospital charges (median, US$50,690 vs US$17,510). Geographically, California and New Jersey were the states with the highest charges, whereas Vermont and Maryland were states with the lowest charges. The study analysis provides a broad sampling of nationwide demographics, LOS, and in-hospital charges for patients with burns and inhalation injury.

Objectives: Oral amoxicillin (50 mg/kg/day) thrice daily is the first-line therapy for non-severe childhood pneumonia. Compliance could be enhanced if two daily doses are employed. We assessed the equivalence of oral amoxicillin (50 mg/kg/day) thrice or twice daily in those patients., Patients and Methods: This randomized (1 : 1), controlled, triple-blinded investigation conducted at one centre in Brazil included children aged 2-59 months with non-severe pneumonia diagnosed by trained paediatricians based on respiratory complaints and radiographic pulmonary infiltrate/consolidation. Participants were randomly assigned to receive one bottle (Amoxicillin 1) at 6 am, 2 pm and 10 pm and the other bottle (Amoxicillin 2) at 8 am and 8 pm: one bottle contained amoxicillin and the other placebo and vice versa. Only the pharmacist knew patients' allocation. Follow-up assessments were done at 2, 5 and 14 days after enrolment. Chest radiographs were read by three independent radiologists. Primary outcome was treatment failure (development of danger signs, persistence of fever, tachypnoea, development of serious adverse reactions, death and withdrawal from the trial) at 48 h. ClinicalTrials.gov: identifier NCT01200706., Results: Four hundred and twelve and 408 participants received amoxicillin thrice or twice daily, respectively. Treatment failure was detected in 94 (22.8%) and 94 (23.0%) patients in intention-to-treat analysis (risk difference 0.2%; 95% CI: -5.5%-6.0%) and in 80 (20.1%) and 85 (21.3%) patients in per-protocol analysis (risk difference 1.2%; 95% CI: -4.4%-6.8%). Pneumonia was radiologically confirmed by concordant reading in 277 (33.8%) cases, among whom treatment failure was registered in 25/133 (18.8%) and 27/144 (18.8%) participants from the thrice and twice daily doses subgroups, respectively (risk difference -0.05%; 95% CI: -9.3%-9.2%)., Conclusions: Oral amoxicillin (50 mg/kg/day) twice daily is as efficacious as thrice daily., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Nitric oxide (NO) was described to inhibit the proliferation of neural stem cells. Some evidence suggests that NO, under certain conditions, can also promote cell proliferation, although the mechanisms responsible for a potential proliferative effect of NO in neural stem cells have remained unaddressed. In this work, we investigated and characterized the proliferative effect of NO in cell cultures obtained from the mouse subventricular zone. We found that the NO donor NOC-18 (10 microM) increased cell proliferation, whereas higher concentrations (100 microM) inhibited cell proliferation. Increased cell proliferation was detected rapidly following exposure to NO and was prevented by blocking the mitogen-activated kinase (MAPK) pathway, independently of the epidermal growth factor (EGF) receptor. Downstream of the EGF receptor, NO activated p21Ras and the MAPK pathway, resulting in a decrease in the nuclear presence of the cyclin-dependent kinase inhibitor 1, p27(KIP1), allowing for cell cycle progression. Furthermore, in a mouse model that shows increased proliferation of neural stem cells in the hippocampus following seizure injury, we observed that the absence of inducible nitric oxide synthase (iNOS(-/-) mice) prevented the increase in cell proliferation observed following seizures in wild-type mice, showing that NO from iNOS origin is important for increased cell proliferation following a brain insult. Overall, we show that NO is able to stimulate the proliferation of neural stem cells bypassing the EGF receptor and promoting cell division. Moreover, under pathophysiological conditions in vivo, NO from iNOS origin also promotes proliferation in the hippocampus.

An inducible system has been established in Nicotiana tabacum plants allowing controlled expression of Sar1-GTP and thus the investigation of protein dynamics after inhibition of endoplasmic reticulum (ER) to Golgi transport. Complete Golgi disassembly and redistribution of Golgi markers into the ER was observed within 18-24h after induction. At the ultrastructural level Sar1-GTP expression led to a decrease in Golgi stack size followed by Golgi fragmentation and accumulation of vesicle remnants. Induction of Sar1-GTP resulted in redistribution of the green fluorescent protein (GFP)-tagged Arabidopsis golgins AtCASP and GC1 (golgin candidate 1, an Arabidopsis golgin 84 isoform) into the ER or cytoplasm, respectively. Additionally, both fusion proteins were observed in punctate structures, which co-located with a yellow fluorescent protein (YFP)-tagged version of Sar1-GTP. The Sar1-GTP-inducible system is compared with constitutive Sar1-GTP expression and brefeldin A treatment, and its potential for the study of the composition of ER exit sites and early cis-Golgi structures is discussed.

Aims: In this study, we propose (i) to study the photodynamic inactivation (PDI) efficiency of neutral and cationic porphyrin derivatives, (ii) to characterize the kinetics of the inactivation process using Bacillus cereus as a model endospore-producing bacterium and (iii) to conclude on the applicability of porphyrin derivatives in the inactivation of bacterial endospores., Methods and Results: The study of PDI of Bacillus cereus endospores, taken as model-endospores, using porphyrin derivatives differing in the number of positive charges and in the meso-substituent groups, showed that neutral, monocationic and dicationic porphyrins are quite ineffective, in contrast with the tri- and tetra-cationic molecules. The most effective porphyrin is a tricationic porphyrin with a meso-pentafluorophenyl group. With this photosensitizer (PS), at 0.5 micromol l(-1), a reduction of 3.5 log units occurs after only 4 min of irradiation. None of the porphyrin derivatives showed toxicity in the absence of light., Conclusions: Some porphyrin derivatives are efficient PSs for the inactivation of bacterial endospores and should be considered in further studies. Small modifications in the substituent groups, in addition to charge, significantly improve the effectiveness of the molecule as a PS for endospore inactivation., Significance and Impact of the Study: Tetrapyrrolic macrocycles should be regarded as worthy to explore for the PDI of spore-producing gram-positive bacteria. The development of molecules, more selective and effective, emerges as a new objective.

A faster and simpler method to monitor the photoinactivation process of Escherichia coli involving the use of recombinant bioluminescent bacteria is described here. Escherichia coli cells were transformed with luxCDABE genes from the marine bioluminescent bacterium Vibrio fischeri and the recombinant bioluminescent indicator strain was used to assess, in real time, the effect of three cationic meso-substituted porphyrin derivatives on their metabolic activity, under artificial (40 W m(-2)) and solar irradiation (approximately 620 W m(-2)). The photoinactivation of bioluminescent E. coli is effective (>4 log bioluminescence decrease) with the three porphyrins used, the tricationic porphyrin Tri-Py+-Me-PF being the most efficient compound. The photoinactivation process is efficient both with solar and artificial light, for the three porphyrins tested. The results show that bioluminescence analysis is an efficient and sensitive approach being, in addition, more affordable, faster, cheaper and much less laborious than conventional methods. This approach can be used as a screening method for bacterial photoinactivation studies in vitro and also for the monitoring of the efficiency of novel photosensitizer molecules. As far as we know, this is the first study involving the use of bioluminescent bacteria to monitor the antibacterial activity of porphyrins under environmental conditions.

Golgins are large coiled-coil proteins that play a role in tethering of vesicles to Golgi membranes and in maintaining the overall structure of the Golgi apparatus. Six Arabidopsis proteins with the structural characteristics of golgins were isolated and shown to locate to Golgi stacks when fused to GFP. Two of these golgin candidates (GC1 and GC2) possess C-terminal transmembrane (TM) domains with similarity to the TM domain of human golgin-84. The C-termini of two others (GC3/GDAP1 and GC4) contain conserved GRAB and GA1 domains that are also found in yeast Rud3p and human GMAP210. GC5 shares similarity with yeast Sgm1p and human TMF and GC6 with yeast Uso1p and human p115. When fused to GFP, the C-terminal domains of AtCASP and GC1 to GC6 localized to the Golgi, showing that they contain Golgi localization motifs. The N-termini, on the other hand, label the cytosol or nucleus. Immuno-gold labelling and co-expression with the cis Golgi Q-SNARE Memb11 resulted in a more detailed picture of the sub-Golgi location of some of these putative golgins. Using two independent assays it is further demonstrated that the interaction between GC5, the TMF homologue, and the Rab6 homologues is conserved in plants.

CNS manifestations are rarely attributable to Schistosoma mansoni infection although systemic distribution of S. mansoni eggs is well recorded. We describe 73 patients aged less than 20 years who presented S. mansoni eggs in the stool or rectal biopsy and IFA and/or HAI positive CSF tests to S. mansoni, and who had neurological signs and symptoms. Paraparesis (54.8 per cent), urinary retention (53.4 per cent), and paraplegia (20.5 per cent) were the most commonly observed CNS manifestations. In the CSF, pleocytosis (range 7-560 WBC/mm3) associated with eosinophilia (85.7 per cent vs. 50.0 per cent, p = 0.02) and elevated protein concentration (96.8 per cent vs. 40.0 per cent, p = 0.00003) were observed. We conclude that in areas of the world where infection by S. mansoni is common, neuroschistosomiasis should be an important diagnostic consideration in children with neurological signs and symptoms.