During the past few decades Acinetobacter baumannii has evolved from being a commensal dweller of health-care facilities to constitute one of the most annoying pathogens responsible for hospitalary outbreaks and it is currently considered one of the most important nosocomial pathogens. In a prevalence study of infections in intensive care units conducted among 75 countries of the five continents, this microorganism was found to be the fifth most common pathogen. Two main features contribute to the success of A. baumannii: (i) A. baumannii exhibits an outstanding ability to accumulate a great variety of resistance mechanisms acquired by different mechanisms, either mutations or acquisition of genetic elements such as plasmids, integrons, transposons, or resistant islands, making this microorganism multi- or pan-drug-resistant and (ii) The ability to survive in the environment during prolonged periods of time which, combined with its innate resistance to desiccation and disinfectants, makes A. baumannii almost impossible to eradicate from the clinical setting. In addition, its ability to produce biofilm greatly contributes to both persistence and resistance. In this review, the pathogenesis of the infections caused by this microorganism as well as the molecular bases of antibacterial resistance and clinical aspects such as treatment and potential future therapeutic strategies are discussed in depth.

Background To date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK). Methods We did a phase 2, open-label, randomised, controlled trial on adults aged 18–60 years, vaccinated with a single dose of ChAdOx1-S 8–12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov ( NCT04860739 ), and is ongoing. Findings Between April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84–85·33) at baseline to 7756·68 BAU/mL (7371·53–8161·96) at day 14 (p<0·0001). IgG against trimeric spike protein increased from 98·40 BAU/mL (95% CI 85·69–112·99) to 3684·87 BAU/mL (3429·87–3958·83). The interventional:control ratio was 77·69 (95% CI 59·57–101·32) for RBD protein and 36·41 (29·31–45·23) for trimeric spike protein IgG. Reactions were mild (n=1210 [68%]) or moderate (n=530 [30%]), with injection site pain (n=395 [88%]), induration (n=159 [35%]), headache (n=199 [44%]), and myalgia (n=194 [43%]) the most commonly reported adverse events. No serious adverse events were reported. Interpretation BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile. Funding Instituto de Salud Carlos III. Translations For the French and Spanish translations of the abstract see Supplementary Materials section.

om as , F e r na n d o G on zález Candelas, SeqCOVID-SPAIN consortium, Tanja Stadler & Richard A. NeherThis is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

Diarrhea is one of the main causes of morbidity and mortality among children in sub-Saharan Africa and one of the main causes of hospital admissions in rural areas. Stool samples were collected from 529 children admitted with diarrhea to the Manhiça District Hospital (September 2000 to September 2001) and processed to detect bacterial enteropathogens, parasites, and virus. Diarrheagenic Escherichia coli, isolated from 120 samples (22.6%; enteroaggregative [corrected] [9.6%], enterotoxigenic [6.8%], enteropathogenic [corrected] [4.3%], and verotoxigenic [1.9%]) was the most frequently isolated pathogen, followed by Ascaris lumbricoides (9.3%). Others detected included Salmonella spp. and Giardia lamblia (2.5% each) and Campylobacter spp. (1.7%). A. lumbricoides (92% versus 8%; P<0.001) and Strongyloides stercolaris (100% versus 0%; P=0.008) were most frequently isolated in children older than 12 months of age. Resistance to trimethoprim-sulphametoxazole and ampicillin was high. Etiologic data on diarrheal diseases and susceptibility patterns of diarrheal pathogens are important tools for clinical management and control strategic planning.

Antimicrobial susceptibility testing (AST) technologies help to accelerate the initiation of targeted antimicrobial therapy for patients with infections and could potentially extend the lifespan of current narrow-spectrum antimicrobials. Although conceptually new and rapid AST technologies have been described, including new phenotyping methods, digital imaging and genomic approaches, there is no single major, or broadly accepted, technological breakthrough that leads the field of rapid AST platform development. This might be owing to several barriers that prevent the timely development and implementation of novel and rapid AST platforms in health-care settings. In this Consensus Statement, we explore such barriers, which include the utility of new methods, the complex process of validating new technology against reference methods beyond the proof-of-concept phase, the legal and regulatory landscapes, costs, the uptake of new tools, reagent stability , optimization of target product profiles, difficulties conducting clinical trials and issues relating to quality and quality control, and present possible solutions.

The role of tyrosine phosphorylation in the regulation of tyrosine protein kinase activity was investigated using site‐directed mutagenesis to alter the structure and environment of the three tyrosine residues present in the C terminus of avian pp60c‐src. Mutations that change Tyr 527 to Phe or Ser activate in vivo tyrosine protein kinase activity and induce cellular transformation of chicken cells in culture. In contrast, alterations of tyrosine residues present at positions 511 or 519 in c‐src do not induce transformation or in vivo tyrosine protein kinase activity. Amber mutations, which alter the structure of the pp60c‐src C terminus by inducing premature termination of the c‐src protein at either residue 518 or 523 also induce morphological transformation and increase in vivo tyrosine phosphorylation, whereas removal of the last four residues of c‐src by chain termination at residue 530 does not alter the kinase activity or the biological activity of the resultant c‐src protein. We conclude from these studies that C‐terminal alterations which either remove or replace Tyr 527 serve to activate the c‐src protein resulting in cellular transformation and increased in vivo tyrosine protein kinase activity.

A total of 451 stool specimens were collected from children less than five years of age with acute diarrhea from Ifakara, Tanzania and processed to detect bacterial enteropathogens, parasites, and rotaviruses. These specimens were divided into 348 from the dry season and 103 from the rainy season. Overall, diarrheogenic Escherichia coli (35.7%) were the predominant enteropathogens, with enterotoxigenic E. coli, enteroaggregative E. coli, and enteropathogenic E. coli being the most prevalent. Moreover, enteroaggregative E. coli (63% versus 35.5%; P < 0.05), Shigella spp. (24% versus 12%; P < 0.05), and rotavirus (23% versus 4%; P < 0.05) were more prevalent in the dry season than in the rainy season and enterotoxigenic E. coli (51.6% versus 20%; P < 0.05) and Giardia lamblia (14% versus 1%; P < 0.05) were more prevalent in the rainy season.

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