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47 ud af 47 tidsskrifter valgt, søgeord (pep) valgt, emner højest 180 dage gamle, sorteret efter nyeste først.
105 emner vises.
Journal of Infectious Diseases, 26.01.2024
Tilføjet 26.01.2024
Abstract Background Severe fever with thrombocytopenia syndrome (SFTS), a lethal tick-borne hemorrhagic fever, prompted our investigation into prognostic predictors and potential drug targets using plasma Olink Proteomics.Methods Employing the Olink assay, we analyzed 184 plasma proteins in 30 survivors and 8 non-survivors of SFTS. Validation was performed in a cohort of 154 SFTS patients using enzyme-linked immunosorbent assay. We utilized the Drug Gene Interaction database to identify protein-drug interactions.Results Non-survivors exhibited 110 differentially expressed proteins (DEPs) compared to survivors, with functional enrichment in the cell chemotaxis-related pathway. Thirteen DEPs, including C-C motif chemokine 20 (CCL20), calcitonin gene-related peptide alpha and Pleiotrophin, were associated with multiple organ dysfunction syndrome. CCL20 emerged as the top predictor of death, demonstrating an area under the curve of 1 (P = .0004) and 0.9033 (P < .0001) in the discovery and validation cohort, respectively. Patients with CCL20 levels exceeding 45.74 pg/mL exhibited a fatality rate of 45.65%, while no deaths occurred in those with lower CCL20 levels. Furthermore, we identified 202 FDA-approved drugs targeting 37 death-related plasma proteins.Conclusions Distinct plasma proteomic profiles characterize SFTS patients with different outcomes, with CCL20 emerging as a novel, sensitive, accurate, and specific biomarker for predicting SFTS prognosis.
Læs mere Tjek på PubMedInfection, 25.01.2024
Tilføjet 25.01.2024
Abstract Purpose Human Borna disease virus (BoDV-1) encephalitis is an emerging disease in Germany. This study investigates the spectrum of human BoDV-1 infection, characterizes anti-BoDV-1-antibodies and kinetics, and compares laboratory test performances. Methods Three hundred four encephalitis cases, 308 nation-wide neuropsychiatric conditions, 127 well-defined psychiatric cases from Borna disease-endemic areas, and 20 persons with contact to BoDV-1 encephalitis patients or animals were tested for BoDV-1 infections by serology and PCR. Results BoDV-1 infections were only found in encephalitis patients with residence in, or recent travel to, virus-endemic areas. Antibodies were detected as early as 12 days after symptom onset. Serum antibody levels correlated with disease duration. Serology was ordered after 50% of the disease duration had elapsed, reflecting low awareness. BoDV-1-antibodies were of IgG1 subclass, and the epitope on BoDV-1 antigens was determined. Specificity of the indirect immunofluorescence antibody test (IFAT) and lineblot (LB) from serum and cerebrospinal fluid (CSF), as well as PCR testing from CSF, was 100%. Sensitivity, depending on first or all samples, reached 75–86% in serum and 92–94% in CSF for the IFAT, and 33–57% in serum and 18–24% in CSF for the LB. Sensitivity for PCR in CSF was 25–67%. Positive predictive values were 100% each, while negative predictive values were 99% (IFAT), 91–97% (LB), and 90% (PCR). Conclusions There is no hint that BoDV-1 causes other diseases than encephalitis in humans. Awareness has to be increased in virus-endemic areas. Tests are robust but lack sensitivity. Detection of IgG1 against specific peptides may facilitate diagnosis. Screening of healthy individuals is likely not beneficial.
Læs mere Tjek på PubMedBMC Infectious Diseases, 25.01.2024
Tilføjet 25.01.2024
Abstract Background Oritavancin, a long-acting lipoglycopeptide approved for use in acute bacterial skin and skin structure infections, has limited data evaluating use in serious infections due to Gram-positive organisms. We aimed to assess the effectiveness and safety of oritavancin for consolidative treatment of Gram-positive bloodstream infections (BSI), including infective endocarditis (IE). Methods We conducted a retrospective cohort study evaluating adult patients admitted to University of Colorado Hospital from March 2016 to January 2022 who received ≥ 1 oritavancin dose for treatment of Gram-positive BSI. Patients were excluded if the index culture was drawn at an outside facility or were > 89 years of age. The primary outcome was a 90-day composite failure (clinical or microbiological failure) in those with 90-day follow-up. Secondary outcomes included individual components of the primary outcome, acute kidney injury (AKI), infusion-related reactions (IRR), and institutional cost avoidance. Results Overall, 72 patients were included. Mean ± SD age was 54 ± 16 years, 61% were male, and 10% had IE. Organisms most commonly causing BSI were Staphylococcus aureus (68%, 17% methicillin-resistant), followed by Streptococcus spp. (26%), and Enterococcus spp. (10%). Patients received standard-of-care antibiotics before oritavancin for a median (IQR) of 11 (5–17) days. Composite failure in the clinically evaluable population (n = 64) at 90-days occurred in 14% and was composed of clinical and microbiological failure, which occurred in 14% and 5% of patients, respectively. Three patients (4%) experienced AKI after oritavancin, and two (3%) experienced an IRR. Oritavancin utilization resulted in earlier discharge for 94% of patients corresponding to an institutional cost-avoidance of $3,055,804 (mean $44,938/patient) from 1,102 hospital days saved (mean 16 days/patient). Conclusions The use of oritavancin may be an effective sequential therapy for Gram-positive BSI to facilitate early discharge resulting in institutional cost avoidance.
Læs mere Tjek på PubMedAnise Nkenjop HappiOlusola Akinola OgunsanyaAkeemat Opeyemi AyinlaAyotunde Elijah SijuwolaFemi Mudasiru SaibuKazeem AkanoCecilia NwofokeObineche Tobias EliasOlivia Achonduh-AtijegbeRichard Olumide DaoduOluwatobi Abel AdedokunAbraham AdeyemoKehinde Ebenezer OgundanaOmolola Zaheedat LawalEdyth ParkerIguosadolo NosamiefanJohnson OkolieZahra F. ParkerMelanie D. McCauleyLeigh Anne EllerKara LombardiAbdulwasiu Bolaji TiamiyuMichael IroezinduEdward AkinwaleThierry Lamare Fouapon Assedi NjatouTsedal MebrahtuErica BroachAnastasia ZuppePetra PrinsJenny LayMihret AmareKayvon ModjarradNatalie D. CollinsSandhya VasanCynthia TuckerSharon DayeChristian Tientcha Happia African Centre of Excellence for Genomics of Infectious Diseases, Redeemer’s University, Ede, Osun State, Nigeriab Redeemer’s University, Ede, Osun, Nigeriac Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeriad University of Nigeria, Nsukka, Nigeriae Scripps Translational Science Institute, La Jolla, CA, USAf Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USAg Henry M. Jackson Foundation Medical Research International Ltd/Gte, Abuja, Nigeriah Emerging Infectious Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USAi One Health Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USAk Viral Diseases Program, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USAl Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, MA, USA
Emerg Microbes Infect, 23.01.2024
Tilføjet 23.01.2024
Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell
PLoS One Infectious Diseases, 23.01.2024
Tilføjet 23.01.2024
by Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu2+ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of metronidazole, vancomycin, and fidaxomicin to kill C. difficile. The activity of metronidazole, which targets DNA, is enhanced by a factor of 32 when combined with p3, previously shown to bind and condense DNA. Conversely, the activity of vancomycin, which acts at bacterial cell walls, is enhanced 64-fold when combined with membrane-active p1-Cu2+. As shown through microscopy monitoring the permeabilization of membranes of C. difficile cells and vesicle mimics of their membranes, the adjuvant effect of p1 and p3 in the apo and holo states is consistent with a mechanism of action where the peptides enable greater antibiotic penetration through the cell membrane to increase their bioavailability. The variations in effects obtained with the different forms of the peptides reveal that while all piscidins generally sensitize C. difficile to antibiotics, co-treatments can be optimized in accordance with the underlying mechanism of action of the peptides and antibiotics. Overall, this study highlights the potential of antimicrobial peptides as antibiotic adjuvants to increase the lethality of currently approved antibiotic dosages, reducing the risk of incomplete treatments and ensuing drug resistance.
Læs mere Tjek på PubMedGabriele Giuliano, Sara Benedetti, Margherita Sambo, Fabio Pierguidi, Mario Tumbarello
Clinical Microbiology and Infection, 20.01.2024
Tilføjet 20.01.2024
We have read with great interest the article written by Wurcel et al. [1] published in Clin Microbiol Infect. We completely agree with the necessity to design randomized clinical trials to investigate the use of long-acting glycopeptides (LGPs) such as those for the treatment of infective endocarditis, which are now allowed off-label use, in comparison with oral therapy in people who inject drugs (PWIDs). We recently managed a 35-years-old man, who was addicted to heroin intravenously and who presented at our Emergency Department for fever and dyspnoea.
Læs mere Tjek på PubMedHai‐Ping Tang, Ya‐Ping He, Jian Wang, Jian‐Min Zhan, Wen‐Bo Lian, Feng Xue, Li Wang, Yijie Li, Ailian Zhang, Fuchun Zhang, Chen Xu, Jinyao Li, Wan‐Xiang Xu
Journal of Medical Virology, 19.01.2024
Tilføjet 19.01.2024
Thomas Karl Atkins, Arnav Solanki, George Vasmatzis, James Cornette, Marc Riedel
Frontiers in Immunology, 16.01.2024
Tilføjet 16.01.2024
Bias in neural network model training datasets has been observed to decrease prediction accuracy for groups underrepresented in training data. Thus, investigating the composition of training datasets used in machine learning models with healthcare applications is vital to ensure equity. Two such machine learning models are NetMHCpan-4.1 and NetMHCIIpan-4.0, used to predict antigen binding scores to major histocompatibility complex class I and II molecules, respectively. As antigen presentation is a critical step in mounting the adaptive immune response, previous work has used these or similar predictions models in a broad array of applications, from explaining asymptomatic viral infection to cancer neoantigen prediction. However, these models have also been shown to be biased toward hydrophobic peptides, suggesting the network could also contain other sources of bias. Here, we report the composition of the networks’ training datasets are heavily biased toward European Caucasian individuals and against Asian and Pacific Islander individuals. We test the ability of NetMHCpan-4.1 and NetMHCpan-4.0 to distinguish true binders from randomly generated peptides on alleles not included in the training datasets. Unexpectedly, we fail to find evidence that the disparities in training data lead to a meaningful difference in prediction quality for alleles not present in the training data. We attempt to explain this result by mapping the HLA sequence space to determine the sequence diversity of the training dataset. Furthermore, we link the residues which have the greatest impact on NetMHCpan predictions to structural features for three alleles (HLA-A*34:01, HLA-C*04:03, HLA-DRB1*12:02).
Læs mere Tjek på PubMedBMC Infectious Diseases, 15.01.2024
Tilføjet 15.01.2024
Keith Feldman, Sarah L. Suppes, Jennifer L. Goldman
PLoS One Infectious Diseases, 12.01.2024
Tilføjet 12.01.2024
by Keith Feldman, Sarah L. Suppes, Jennifer L. Goldman Documentation of adverse drug reactions (ADRs) is a key factor in guiding future prescribing. However, incomplete documentation is common and often fails to distinguish implicated drugs as true allergies. This in turn leads to unnecessary avoidance of implicated drug classes and may result in sub-optimal prescribing. Pharmacovigilance (PV) programs utilize a systematic approach to clarify ADR documentation and are known to improve patient safety. Yet it remains unclear if PV alters prescribing. Or, if the existence of the ADR documentation itself continues to prompt avoidance of implicated drugs. To address this, our work presents a retrospective cohort study assessing if clarification of antibiotic ADRs by a hospital-wide PV team was associated with future, safe, re-prescribing at a freestanding pediatric hospital in the midwestern United States. First, we compared the likelihood of future prescribing in an antibiotic class with an active ADR, as compared to alternative drug classes, between PV-clarified and non-clarified patients. Second, we assessed differences in adverse event rates 30-days after future prescribing based on PV clarification status. For robustness, analyses were performed on patients with ADRs in four antibiotic classes: penicillin-based beta-lactams (n = 45,642), sulfonamides/trimethoprim (n = 5,329), macrolides (n = 3,959), and glycopeptides (n = 622). Results illustrate that clarification of an ADR by PV was associated with an increased odds of future prescribing in the same drug class (Odds Ratio [95%-CI]): penicillin-based beta-lactams (1.59 [1.36–1.89]), sulfonamides/trimethoprim (2.29 [0.89–4.91]), macrolides (0.77 [0.33–1.61]), and glycopeptide (1.85 [1.12–3.20]). Notably, patients clarified by PV experienced no increase in the rate of adverse events within 30-days following the prescribing of antibiotics in the same class as an active ADR. Overall, this study provides strong evidence that PV reviews safely increase the rate of re-prescribing antibiotics even in the presence of an existing implicated drug ADR.
Læs mere Tjek på PubMedVictoria R. Adams, Leonard B. Collins, Taufika Islam Williams, Jennifer Holmes, Paul Hess, Hannah M. Atkins, Grace Scheidemantle, Xiaojing Liu, Mareca Lodge, Aaron J. Johnson, Arion Kennedy
Frontiers in Immunology, 11.01.2024
Tilføjet 11.01.2024
Background & aimsActivated CD8+ T cells are elevated in Nonalcoholic steatohepatitis (NASH) and are important for driving fibrosis and inflammation. Despite this, mechanisms of CD8+ T cell activation in NASH are largely limited. Specific CD8+ T cell subsets may become activated through metabolic signals or cytokines. However, studies in NASH have not evaluated the impact of antigen presentation or the involvement of specific antigens. Therefore, we determined if activated CD8+ T cells are dependent on MHC class I expression in NASH to regulate fibrosis and inflammation. MethodsWe used H2Kb and H2Db deficient (MHC I KO), Kb transgenic mice, and myeloid cell Kb deficient mice (LysM Kb KO) to investigate how MHC class I impacts CD8+ T cell function and NASH. Flow cytometry, gene expression, and histology were used to examine hepatic inflammation and fibrosis. The hepatic class I immunopeptidome was evaluated by mass spectrometry. ResultsIn NASH, MHC class I isoform H2Kb was upregulated in myeloid cells. MHC I KO demonstrated protective effects against NASH-induced inflammation and fibrosis. Kb mice exhibited increased fibrosis in the absence of H2Db while LysM Kb KO mice showed protection against fibrosis but not inflammation. H2Kb restricted peptides identified a unique NASH peptide Ncf2 capable of CD8+ T cell activation in vitro. The Ncf2 peptide was not detected during fibrosis resolution. ConclusionThese results suggest that activated hepatic CD8+ T cells are dependent on myeloid cell MHC class I expression in diet induced NASH to promote inflammation and fibrosis. Additionally, our studies suggest a role of NADPH oxidase in the production of Ncf2 peptide generation.
Læs mere Tjek på PubMedTassembedo, Souleymane; Mwiya, Mwiya; Mennecier, Anais; Kankasa, Chipepo; Fao, Paulin; Molès, Jean Pierre; Kania, Dramane; Chunda-Liyoka, Catherine; Sakana, Leticia Delphine; D’Ottavi, Morgana; Taofiki, Ajani Ousmane; Rutagwera, David; Wilfried-Tonga, MM; Tylleskär, Thorkild; Nagot, Nicolas; Van De Perre, Philippe
AIDS, 9.01.2024
Tilføjet 9.01.2024
Objective: Our study aimed to assess the PMTCT indicators in Burkina Faso and Zambia using a patient-orientated innovative strategy based on the second visit in the Expanded Program on Immunization (EPI-2) visit at 6–8 weeks. Design: This was a cross sectional study. Methods: We assessed women attending EPI-2 at primary healthcare facilities in Burkina Faso and Zambia with their children about their exposure to PMTCT interventions. For women living with HIV (WLHIV), viral load was measured and their children were tested for HIV DNA using point of care devices. Results: Overall, 25 093 were enrolled from Burkina Faso and 8961 women from Zambia. Almost, all women attended at least one antenatal care visit. Among those aware of their HIV-positive status, 95.8 and 99.2% were on antiretroviral therapy (ART) in Burkina Faso and Zambia, respectively. Among WLHIV on ART, 75 and 79.2% achieved a viral load suppression (viral load
Læs mere Tjek på PubMedBMC Infectious Diseases, 2.01.2024
Tilføjet 2.01.2024
Abstract Background Severe pneumonia frequently causes irreversible sequelae and represents a major health burden for children under the age of 5. Matrix Metallopeptidase 9 (MMP9) is a zinc-dependent endopeptidase that is involved in various cellular processes. The correlation between MMP9 and the risk of severe childhood pneumonia remains unclear. Methods Here we assemble a case–control cohort to study the association of genetic variants in MMP9 gene with severe childhood pneumonia susceptibility in a Southern Chinese population (1034 cases and 8426 controls). Results Our results indicate that the allele G in rs3918262 SNP was significantly associated with an increased risk of severe pneumonia. Bioinformatic analyses by expression quantitative trait loci (eQTL), RegulomeDB and FORGEdb database analysis showed that rs3918262 SNP has potential regulatory effect on translational efficiency and protein level of MMP9 gene. Furthermore, MMP9 concentrations were significantly up-regulated in the bronchoalveolar lavages (BALs) of children with severe pneumonia. Conclusion In summary, our findings suggest that MMP9 is a novel predisposing gene for childhood pneumonia.
Læs mere Tjek på PubMedSalama, H. Z., Alnajjar, Y. A., Owais, T. A., Jobran, A. W. M., Safi, R., Bahar, M., Al-Ashhab, H.
BMJ Open, 28.12.2023
Tilføjet 28.12.2023
ObjectiveTo evaluate the utilisation and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) procedures, success rates, incidence and risk factors for procedural-related complications in a single centre-based study. Study designRetrospective cohort study. SettingFirst advanced tertiary endoscopy centre in Palestine. ParticipantsA total of 1909 procedures on 1303 patients were included in the analysis: females were 57.9% of the cases (n=755), 1225 patients (94%) were from West Bank and Jerusalem and 78 (6%) were from Gaza Strip. All patients who underwent ERCP throughout the period from December 2017 to September 2022 were selected to participate in the study. Primary and secondary outcome measuresThe primary outcomes of interest in our analysis were success rates, procedural outcomes and post- procedural complications including pancreatitis, bleeding and others. Two multivariate logistic regression models were performed to calculate the risk of post-ERCP complications and post-ERCP pancreatitis (PEP) in patients with certain risk factors like demographic factors, procedural techniques\' variation, pancreatic duct manipulations and others. We also discussed the management of the failed procedures. ResultsThe overall complication rate was 5%, including PEP (n=43, 2.3%), infection/cholangitis (n=20, 1%), bleeding (n=9, 0.5%) and perforation (n=7, 0.4%). The mortality rate was 0.6% (n=11). Risk factors for adverse events included pancreatic duct cannulation and PEP (p
Læs mere Tjek på PubMedHamad AlRashed, Johanna Miele, Joshua Prasad, Deborah Adenikinju, Chukwuemeka Iloegbu, John Patena, Dorice Vieira, Joyce Gyamfi, Emmanuel Peprah
PLoS One Infectious Diseases, 28.12.2023
Tilføjet 28.12.2023
by Hamad AlRashed, Johanna Miele, Joshua Prasad, Deborah Adenikinju, Chukwuemeka Iloegbu, John Patena, Dorice Vieira, Joyce Gyamfi, Emmanuel Peprah Aim and objectives The aim of this study was to conduct a systematic review analysis to identify and evaluate the available literature on implementation science outcomes research in relation to End Stage Renal Disease (ESRD) in Pakistan. Methods A systematic database search of PubMed, Web of Science, EMBASE, Cochrane Library, CINAHL, and Ovid was conducted through October 22nd, 2022, without any restrictions on publication dates. A screening and data extraction tool, Covidence, was used to evaluate the literature against our inclusion and exclusion criteria. Furthermore, a Mixed Methods Appraisal Tool (MMAT) was used to evaluate the selected studies. Results We identified four studies that presented findings of implementation outcomes research which were related to appropriateness, feasibility, and acceptability. Appropriateness was examined using knowledge scores (p = 0.022) and medication adherence scores (p < 0.05) that showed statistical significance between the control and intervention groups. Acceptability was assessed through a cross sectional quantitative descriptive study that evaluated the reasons for refusal and acceptance of treatment in a cohort of patients suffering from ESRD. Feasibility was examined in one cross sectional, and one mixed methods study that aimed to evaluate and understand the impact of initiating dialysis treatment and the feasibility of maintaining it in low-income families that care for children or adults with ESRD. Conclusion The preliminary results of this review indicate a gap in the availability of implementation research studies about ESRD in Pakistan. The burden of ESRD, and the implementation methods by which it is treated is notable in Pakistan and requires evidence-based measures to be implemented to support the critical healthcare delivery platforms that provide treatment.
Læs mere Tjek på PubMedSophie LiuuMalgorzata NepelskaHélène PfisterJoao Gamelas MagalhaesGregoire ChevalierFrancesco StrozziColine BillereyMarc MarescaCendrine NicolettiEric Di PasqualeCharlie PechardLaureen BardouilletStephen E. GirardinIvo Gomperts BonecaJoel DoréHervé M. BlottièreChristophe BonnyLaurent CheneAntonietta CultroneaEnterome, Paris 75011, FrancebInstitut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AgroParisTech, Food Microbial Ecology lab (Micalis), Université Paris-Saclay, Jouy-en-Josas 78350, FrancecCNRS, Centrale Marseille, Institut des Sciences Moléculaires (iSm2) UMR7313, Aix Marseille Université, Marseille 13013, FrancedInstitut de NeuroPhysioPathologie (INP), Aix Marseille Université, UMR 7051, Marseille 13005, FranceeDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, CanadafInstitut Pasteur, Université Paris Cité, CNRS Unité Mixe de Recherche 6047, INSERM U1306, Unité de Biologie et génétique de la paroi bactérienne, Paris 75015, FrancegInstitut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis, Université Paris-Saclay, Jouy-en-Josas 78350, France
Proceedings of the National Academy of Sciences, 27.12.2023
Tilføjet 27.12.2023
Proceedings of the National Academy of Sciences, Volume 120, Issue 52, December 2023.
Læs mere Tjek på PubMedDavid R. SanninoFrancine A. ArroyoCharles Pepe-RanneyWenbo ChenJean-Marie VollandNathalie H. ElisabethEsther R. AngertaDepartment of Microbiology, Cornell University, Ithaca, NY 14853bSoil & Crop Sciences Section, School of Integrative Plant Sciences, Cornell University, Ithaca, NY 14853cLaboratory for Research in Complex Systems, Menlo Park, CA 94025dDepartment of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA 94720eDepartment of Energy Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720
Proceedings of the National Academy of Sciences, 27.12.2023
Tilføjet 27.12.2023
Proceedings of the National Academy of Sciences, Volume 120, Issue 52, December 2023.
Læs mere Tjek på PubMedNene Kaah Keneh, Sebastien Kenmoe, Arnol Bowo-Ngandji, Jane-Francis Tatah Kihla Akoachere, Hortense Gonsu Kamga, Roland Ndip Ndip, Jean Thierry Ebogo-Belobo, Cyprien Kengne-Ndé, Donatien Serge Mbaga, Nicholas Tendongfor, Lucy Mande Ndip, Seraphine Nkie Esemu
PLoS One Infectious Diseases, 23.12.2023
Tilføjet 23.12.2023
by Nene Kaah Keneh, Sebastien Kenmoe, Arnol Bowo-Ngandji, Jane-Francis Tatah Kihla Akoachere, Hortense Gonsu Kamga, Roland Ndip Ndip, Jean Thierry Ebogo-Belobo, Cyprien Kengne-Ndé, Donatien Serge Mbaga, Nicholas Tendongfor, Lucy Mande Ndip, Seraphine Nkie Esemu Background The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has increased and poses a significant threat to human and animal health in Cameroon and the world at large. MRSA strains have infiltrated various settings, including hospitals, communities, and livestock, contributing to increased morbidity, treatment costs, and mortality. This evidence synthesis aims to understand MRSA prevalence, resistance patterns, and genetic characterization in Cameroon. Methods The methodology was consistent with the PRISMA 2020 guidelines. Studies of any design containing scientific data on MRSA prevalence, genetic diversity, and antimicrobial resistance patterns in Cameroon were eligible for inclusion, with no restrictions on language or publication date. The search involved a comprehensive search strategy in several databases including Medline, Embase, Global Health, Web of Science, African Index Medicus, and African Journal Online. The risk of bias in the included studies was assessed using the Hoy et al tool, and the results were synthesized and presented in narrative synthesis and/or tables and graphs. Results The systematic review analyzed 24 studies, mostly conducted after 2010, in various settings in Cameroon. The studies, characterized by moderate to low bias, revealed a wide prevalence of MRSA ranging from 1.9% to 46.8%, with considerable variation based on demographic and environmental factors. Animal (0.2%), food (3.2% to 15.4%), and environmental samples (0.0% to 34.6%) also showed a varied prevalence of MRSA. The genetic diversity of MRSA was heterogeneous, with different virulence gene profiles and clonal lineages identified in various populations and sample types. Antimicrobial resistance rates showed great variability in the different regions of Cameroon, with notable antibiotic resistance recorded for the beta-lactam, fluoroquinolone, glycopeptide, lincosamide, and macrolide families. Conclusion This study highlights the significant variability in MRSA prevalence, genetic diversity, and antimicrobial resistance patterns in Cameroon, and emphasizes the pressing need for comprehensive antimicrobial stewardship strategies in the country.
Læs mere Tjek på PubMedGaumer, G., Crown, W. H., Kates, J., Luan, Y., Hariharan, D., Jordan, M., Hurley, C. L., Nandakumar, A.
BMJ Open, 22.12.2023
Tilføjet 22.12.2023
ObjectivesThis study examined whether the US President’s Emergency Plan for AIDS Relief (PEPFAR) funding had effects beyond HIV, specifically on several measures of maternal and child health in low-income and middle-income countries (LMICs). The results of previous research on the question of PEPFAR health spillovers have been inconsistent. This study, using a large, multicountry panel data set of 157 LMICs including 90 recipient countries, adds to the literature. DesignSeven indicators including child and maternal mortality, several child vaccination rates and anaemia among childbearing-age women are important population health indicators. Panel data and difference-in-differences estimators (DID) were used to estimate the impact of the PEPFAR programme from inception in 2004 to 2018 using a comparison group of 67 LMICs. Several different models of baseline (2004) covariates were used to help balance the comparison and treatment groups. Staggered DID was used to estimate impacts since all countries did not start receiving aid at PEPFAR’s inception. SettingAll 157 LMICs from 1990 to 2018. Participants90 LMICs receiving PEPFAR aid and cohorts of those countries, including those required to submit annual country operational plans (COP), other recipient countries (non-COP), and three groupings of countries based on cumulative amount of per capita aid received (high, medium, low). InterventionsPEPFAR aid to combat the HIV epidemic. Primary outcome measuresMaternal mortality and child mortality rates, vaccination rates to protect children for diphtheria, whooping cough and tetanus, measles, HepB3, and tetanus, and prevalence of anaemia in women of childbearing age. ResultsAcross PEPFAR recipient countries, large, favourable PEPFAR health effects were found for rates of childhood immunisation, child mortality and maternal mortality. These beneficial health effects were large and significant in all segments of PEPFAR recipient countries studied. We also found significant and favourable programme effects on the prevalence of anaemia in women of childbearing age in PEPFAR recipient countries receiving the most intensive financial support from the PEPFAR programme. Other recipient countries did not demonstrate significant effects on anaemia. ConclusionsThis study demonstrated that important health indicators, beyond HIV, have been consistently and favourably influenced by PEPFAR presence. Child and maternal mortality have been substantially reduced, and childhood immunisation rates increased. We also found no evidence of ‘crowding out’ or negative spillovers in these resource-poor countries. These findings add to the body of evidence that PEPFAR has had favourable health effects beyond HIV. The implications of these findings are that foreign aid for health in one area may have favourable health effects in other areas in recipient countries. More research is needed on the influence of the mechanisms at work that create these spillover health effects of PEPFAR.
Læs mere Tjek på PubMedVaidehi Rajguru, Stuti Chatterjee, Shambhavi Garde, Manjula Reddy
Trends in Microbiology, 10.12.2023
Tilføjet 10.12.2023
Peptidoglycan (PG) is a protective mesh-like polymer in bacterial cell walls that enables their survival in almost every ecological niche. PG is formed by crosslinking of several glycan strands through short peptides, conferring a characteristic structure and elasticity, distinguishing it from other polymeric exoskeletons. The significance of PG crosslink formation has been known for decades, as some of the most widely used antibiotics, namely β-lactams, target the enzymes that catalyze this step. However, the importance of crosslink hydrolysis in PG biology remained largely underappreciated. Recent advances demonstrate the functions of crosslink cleavage in diverse physiological processes, including an indispensable role in PG expansion during the cell cycle, thereby making crosslink cleaving enzymes an untapped target for novel drugs. Here, we elaborate on the fundamental roles of crosslink-specific endopeptidases and their regulation across the bacterial kingdom.
Læs mere Tjek på PubMedJonathan BakerHugo OmbredaneLeah DalyIan KnowlesGarth RapeportKazuhiro Ito1National Heart and Lung Institute, Imperial College, London, United Kingdom2Pharmidex, London, United Kingdom, Miguel Angel Martinez
Antimicrobial Agents And Chemotherapy, 9.12.2023
Tilføjet 9.12.2023
FEMS Microbiology Reviews, 6.12.2023
Tilføjet 6.12.2023
Abstract Small proteins comprising less than 100 amino acids have been often ignored in bacterial genome annotations. About 10 years ago, focused efforts started to investigate whole peptidomes, which resulted in the discovery of a multitude of small proteins, but only a number of them have been characterized in detail. Generally, small proteins can be either membrane or cytosolic proteins. The latter interact with larger proteins, RNA or even metal ions. Here, we summarize our current knowledge on small proteins from Gram-positive bacteria with a special emphasis on the model organism Bacillus subtilis. Our examples include membrane-bound toxins of type I toxin-antitoxin systems, proteins that block the assembly of higher order structures, regulate sporulation or modulate the RNA degradosome. We do not consider antimicrobial peptides. Furthermore, we present methods for the identification and investigation of such proteins.
Læs mere Tjek på PubMedKayo Suzuki, Daiju Iwata, Kenichi Namba, Keitaro Hase, Miki Hiraoka, Miyuki Murata, Nobuyoshi Kitaichi, Richard Foxton, Susumu Ishida
PLoS One Infectious Diseases, 29.11.2023
Tilføjet 29.11.2023
by Kayo Suzuki, Daiju Iwata, Kenichi Namba, Keitaro Hase, Miki Hiraoka, Miyuki Murata, Nobuyoshi Kitaichi, Richard Foxton, Susumu Ishida Purpose Angiopoietin (Ang) 2 is released from vascular endothelial cells by the stimulation of vascular endothelial growth factor (VEGF)A. Ang2 increases the expression of leukocyte adhesion molecules on endothelial cells via nuclear factor κB. The aim of this study was to evaluate the effects of Ang2 and VEGFA on ocular autoimmune inflammation. Methods We measured the concentrations of Ang2 and VEGFA in vitreous samples among patients with uveitis. Vitreous samples were collected from 16 patients with idiopathic uveitis (uveitis group) and 16 patients with non-inflammatory eye disease (control group). Experimental autoimmune uveoretinitis (EAU) was induced in B10.BR mice with a human interphotoreceptor retinoid-binding protein-derived peptide. The retinochoroidal tissues of the EAU mice were removed, and the mRNA levels of Ang2 and VEGFA were examined. EAU mice treated with anti-Ang2, anti-VEGFA, a combination of anti-Ang2 and anti-VEGFA, anti-Ang2/VEGFA bispecific, or IgG control antibodies were clinically and histopathologically evaluated. Results The protein levels of Ang2 and VEGFA were significantly higher in the vitreous samples of patients with uveitis than in controls (P
Læs mere Tjek på PubMedMingjie JinSiyu LiangJing WangHuihui ZhangYueling ZhangWanjiang ZhangSiguo LiuFang XieState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Virulence, 28.11.2023
Tilføjet 28.11.2023
FEMS Microbiology Reviews, 28.11.2023
Tilføjet 28.11.2023
AbstractThe ever-growing repertoire of genomic techniques continues to expand our understanding of the true diversity and richness of prokaryotic genomes. Riboproteogenomics laid the foundation for dynamic studies of previously overlooked genomic elements. Most strikingly, bacterial genomes were revealed to harbor robust repertoires of small open reading frames (sORFs) encoding a diverse and broadly expressed range of small proteins, or sORF-encoded polypeptides (SEPs). In recent years, continuous efforts led to great improvements in the annotation and characterization of such proteins, yet many challenges remain to fully comprehend the pervasive nature of small proteins and their impact on bacterial biology. In this work, we review the recent developments in the dynamic field of bacterial genome reannotation, catalog the important biological roles carried out by small proteins and identify challenges obstructing the way to full understanding of these elusive proteins.
Læs mere Tjek på PubMedShun Tomita, Kyohei Kuroda, Takashi Narihiro
PLoS One Infectious Diseases, 28.11.2023
Tilføjet 28.11.2023
by Shun Tomita, Kyohei Kuroda, Takashi Narihiro Biological control agents (BCAs), beneficial organisms that reduce the incidence or severity of plant disease, have been expected to be alternatives to replace chemical pesticides worldwide. To date, BCAs have been screened by culture-dependent methods from various environments. However, previously unknown BCA candidates may be buried and overlooked because this approach preferentially selects only easy-to-culture microbial lineages. To overcome this limitation, as a small-scale test case, we attempted to explore novel BCA candidates by employing the shotgun metagenomic information of the activated sludge (AS) microbiome, which is thought to contain unutilized biological resources. We first performed genome-resolved metagenomics for AS taken from a municipal sewage treatment plant and obtained 97 nonribosomal peptide synthetase (NRPS)/polyketide synthase (PKS)-related gene sequences from 43 metagenomic assembled bins, most of which were assigned to the phyla Proteobacteria and Myxococcota. Furthermore, these NRPS/PKS-related genes are predicted to be novel because they were genetically dissimilar to known NRPS/PKS gene clusters. Of these, the condensation domain of the syringomycin-related NRPS gene cluster was detected in Rhodoferax- and Rhodocyclaceae-related bins, and its homolog was found in previously reported AS metagenomes as well as the genomes of three strains available from the microbial culture collections, implying their potential BCA ability. Then, we tested the antimicrobial activity of these strains against phytopathogenic fungi to investigate the potential ability of BCA by in vitro cultivation and successfully confirmed the actual antifungal activity of three strains harboring a possibly novel NRPS gene cluster. Our findings provide a possible strategy for discovering novel BCAs buried in the environment using genome-resolved metagenomics.
Læs mere Tjek på PubMedLucie Barthe, Vanessa Soldan, Luis F. Garcia-Alles
PLoS One Infectious Diseases, 28.11.2023
Tilføjet 28.11.2023
by Lucie Barthe, Vanessa Soldan, Luis F. Garcia-Alles Bacterial micro-compartments (BMC) are complex macromolecular assemblies that participate in varied metabolic processes in about 20% of bacterial species. Most of these organisms carry BMC genetic information organized in operons that often include several paralog genes coding for components of the compartment shell. BMC shell constituents can be classified depending on their oligomerization state as hexamers (BMC-H), pentamers (BMC-P) or trimers (BMC-T). Formation of hetero-oligomers combining different protein homologs is theoretically feasible, something that could ultimately modify BMC shell rigidity or permeability, for instance. Despite that, it remains largely unknown whether hetero-oligomerization is a widespread phenomenon. Here, we demonstrated that the tripartite GFP (tGFP) reporter technology is an appropriate tool that might be exploited for such purposes. Thus, after optimizing parameters such as the size of linkers connecting investigated proteins to GFP10 or GFP11 peptides, the type and strength of promoters, or the impact of placing coding cassettes in the same or different plasmids, homo-oligomerization processes could be successfully monitored for any of the three BMC shell classes. Moreover, the screen perfectly reproduced published data on hetero-association between couples of CcmK homologues from Syn. sp. PCC6803, which were obtained following a different approach. This study paves the way for mid/high throughput screens to characterize the extent of hetero-oligomerization occurrence in BMC-possessing bacteria, and most especially in organisms endowed with several BMC types and carrying numerous shell paralogs. On the other hand, our study also unveiled technology limitations deriving from the low solubility of one of the components of this modified split-GFP approach, the GFP1-9.
Læs mere Tjek på PubMedShanjana AwasthiBhupinder SinghVijay RamaniNachiket M. GodboleCatherine King 1 Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA , Kimberly A. Kline
Infection and Immunity, 27.11.2023
Tilføjet 27.11.2023
Claudia Tandler, Jonas S. Heitmann, Tanja M. Michel, Maddalena Marconato, Simon U. Jaeger, Christian M. Tegeler, Monika Denk, Marion Richter, Melek Tutku Oezbek, Yacine Maringer, Sarah M. Schroeder, Nicole Schneiderhan-Marra, Karl-Heinz Wiesmüller, Michael Bitzer, Natalia Ruetalo, Michael Schindler, Christoph Meisner, Imma Fischer, Hans-Georg Rammensee, Helmut R. Salih, Juliane S. Walz
International Journal of Infectious Diseases, 26.11.2023
Tilføjet 26.11.2023
During the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), different vaccines have been successfully developed [1-3]. Although neutralizing antibodies provide the first line of antiviral defense [4, 5], spike-specific antibody titers tend to wane quickly and show limited neutralizing activity against newly arising variants of concern (VOCs) [6]. In contrast, T cells were shown to mediate long-term immunity that is largely conserved against VOCs after SARS-CoV-2 infection and vaccination [4, 7].
Læs mere Tjek på PubMedTadsanee Awang, Phoom Chairatana, Prapasiri Pongprayoon
PLoS One Infectious Diseases, 22.11.2023
Tilføjet 22.11.2023
by Tadsanee Awang, Phoom Chairatana, Prapasiri Pongprayoon Human α-defensin 5 (HD5) is a cationic antimicrobial peptide exhibiting a wide range of antimicrobial activities. It plays an important role in mucosal immunity of the small intestine. HD5 exerts its bactericidal activities through multiple mechanisms, one of which involves HD5 inducing the formation of pores in the bacterial membrane, subsequently allowing the peptide to enter the bacterial cytoplasm. Nevertheless, the precise molecular intricacies underlying its bactericidal mechanisms remain inadequately understood. In this work, the Potential of Mean Force (PMF) was computed to delve into the energetic properties governing the movement of HD5 across the lipopolysaccharide (LPS) membrane, which is a representative model of the gram-negative bacterial membrane. Our findings indicate that the most favorable free energy is attained when HD5 binds to the surface of the LPS membrane. This favorable interaction is primarily driven by the strong interactions between arginine residues in HD5 and the charged head groups of LPS, serving as the predominant forces facilitating the adhesion of HD5 to the membrane. Our analysis reveals that a dimeric form of HD5 alone is sufficient to create a water-filled channel in the membrane; however, achieving the complete lysis of the gram-negative bacterial membrane requires higher-order oligomerization of HD5. Our results suggest that HD5 employs the toroidal pore formation mechanism to disrupt the integrity of the LPS membrane. Furthermore, we identified that the primary energy barrier obstructing HD5 from traversing the membrane is localized within the hydrophobic core of the membrane, which is also observed for other defensins. Additionally, our study demonstrates that a mixture of HD5-LPS leads to a thinning of the membrane. Taken together, this work provides a deeper insight into the molecular intricacies governing the behavior of HD5 as it translocates through the gram-negative bacterial membrane.
Læs mere Tjek på PubMedLinda Eva Amoah, Kwame Kumi Asare, Donu Dickson, Joana Abankwa, Abena Busayo, Dorcas Bredu, Sherifa Annan, George Adu Asumah, Nana Yaw Peprah, Alexander Asamoah, Keziah Laurencia Malm
PLoS One Infectious Diseases, 16.11.2023
Tilføjet 16.11.2023
by Linda Eva Amoah, Kwame Kumi Asare, Donu Dickson, Joana Abankwa, Abena Busayo, Dorcas Bredu, Sherifa Annan, George Adu Asumah, Nana Yaw Peprah, Alexander Asamoah, Keziah Laurencia Malm
Læs mere Tjek på PubMedFarhana Boby, Md. Nurul Huda Bhuiyan, Barun Kanti Saha, Subarna Sandhani Dey, Anik Kumar Saha, Md Jahidul Islam, Mahci Al Bashera, Shyama Prosad Moulick, Farhana Jahan, Md. Asad Uz Zaman, Sanjana Fatema Chowdhury, Showti Raheel Naser, Md. Salim Khan, Md. Murshed Hasan Sarkar
PLoS One Infectious Diseases, 16.11.2023
Tilføjet 16.11.2023
by Farhana Boby, Md. Nurul Huda Bhuiyan, Barun Kanti Saha, Subarna Sandhani Dey, Anik Kumar Saha, Md Jahidul Islam, Mahci Al Bashera, Shyama Prosad Moulick, Farhana Jahan, Md. Asad Uz Zaman, Sanjana Fatema Chowdhury, Showti Raheel Naser, Md. Salim Khan, Md. Murshed Hasan Sarkar The raising concern of drug resistance, having substantial impacts on public health, has instigated the search of new natural compounds with substantial medicinal activity. In order to find out a natural solution, the current study has utilized prodigiosin, a linear tripyrrole red pigment, as an active ingredient to control bacterial proliferation and prevent cellular oxidation caused by ROS (Reactive Oxygen Species). A prodigiosin-producing bacterium BRL41 was isolated from the ancient Barhind soil of BCSIR Rajshahi Laboratories, Bangladesh, and its morphological and biochemical characteristics were investigated. Whole genome sequencing data of the isolate revealed its identity as Serratia sp. and conferred the presence of prodigiosin gene cluster in the bacterial genome. “Prodigiosin NRPS”, among the 10 analyzed gene clusters, showed 100% similarity with query sequences where pigC, pigH, pigI, and pigJ were identified as fundamental genes for prodigiosin biosynthesis. Some other prominent clusters for synthesis of ririwpeptides, yersinopine, trichrysobactin were also found in the chromosome of BRL41, whilst the rest displayed less similarity with query sequences. Except some first-generation beta-lactam resistance genes, no virulence and resistance genes were found in the genome of BRL41. Structural illumination of the extracted red pigment by spectrophotometric scanning, Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and change of color at different pH solutions verified the identity of the isolated compound as prodigiosin. Serratia sp. BRL41 attained its maximum productivity 564.74 units/cell at temperature 30˚C and pH 7.5 in two-fold diluted nutrient broth medium. The compound exhibited promising antibacterial activity against Gram-positive and Gram-negative bacteria with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values ranged from 3.9 to15.62 μg/mL and 7.81 to 31.25 μg/mL respectively. At concentration 500 μg/mL, except in Salmonella enterica ATCC-10708, prodigiosin significantly diminished biofilm formed by Listeria monocytogens ATCC-3193, Pseudomonas aeruginosa ATCC-9027, Escherichia coli (environmental isolate), Staphylococcus aureus (environmental isolate). Cellular glutathione level (GSH) was elevated upon application of 250 and 500 μg/mL pigment where 125 μg/mL failed to show any free radical scavenging activity. Additionally, release of cellular components in growth media of both Gram-positive and Gram-negative bacteria were facilitated by the extract that might be associated with cell membrane destabilization. Therefore, the overall findings of antimicrobial, antibiofilm and antioxidant activities suggest that in time to come prodigiosin might be a potential natural source to treat various diseases and infections.
Læs mere Tjek på PubMedMasooma Hammad, Hazrat Ali, Noor Hassan, Abdul Tawab, Mahwish Salman, Iqra Jawad, Anne de Jong, Claudia Munoz Moreno, Oscar P. Kuipers, Yusra Feroz, Muhammad Hamid Rashid
PLoS One Infectious Diseases, 15.11.2023
Tilføjet 15.11.2023
by Masooma Hammad, Hazrat Ali, Noor Hassan, Abdul Tawab, Mahwish Salman, Iqra Jawad, Anne de Jong, Claudia Munoz Moreno, Oscar P. Kuipers, Yusra Feroz, Muhammad Hamid Rashid Development of natural, broad-spectrum, and eco-friendly bio-fungicides is of high interest in the agriculture and food industries. In this context, Bacillus genus has shown great potential for producing a wide range of antimicrobial metabolites against various pathogens. A Bacillus velezensis strain FB2 was isolated from an agricultural field of National Institute for Biotechnology and Genetic Engineering (NIBGE) Faisalabad, Pakistan, exhibiting good antifungal properties. The complete genome of this strain was sequenced, and its antifungal potential was assayed by dual culture method. Moreover, structural characterization of its antifungal metabolites, produced in vitro, were studied. Genome analysis and mining revealed the secondary metabolite gene clusters, encoding non-ribosomal peptides (NRPs) production (e.g., surfactin, iturin and fengycin) and polyketide (PK) synthesis (e.g., difficidin, bacillaene and macrolactin). Furthermore, the Bacillus velezensis FB2 strain was observed to possess in vitro antifungal activity; 41.64, 40.38 and 26% growth inhibition against major fungal pathogens i.e. Alternaria alternata, Fusarium oxysporum and Fusarium solani respectively. Its lipopeptide extract obtained by acid precipitation method was also found effective against the above-mentioned fungal pathogens. The ESI-MS/MS analysis indicated various homologs of surfactin and iturin-A, responsible for their antifungal activities. Overall, this study provides a better understanding of Bacillus velezensis FB2, as a promising candidate for biocontrol purposes, acting in a safe and sustainable way, to control plant pathogens.
Læs mere Tjek på PubMedJournal of the American Medical Association, 15.11.2023
Tilføjet 15.11.2023
This Viewpoint discusses the importance of the US Congress reauthorizing funding for the President’s Emergency Plan for AIDS Relief, a program developed in 2003 that has played a critical role in fighting HIV/AIDS worldwide as well as other emerging infections and noncommunicable diseases.
Læs mere Tjek på PubMedBMC Infectious Diseases, 14.11.2023
Tilføjet 14.11.2023
Abstract Background Pro–b-type natriuretic peptide (Pro-BNP) is an inflammatory marker that indicates cardiac damage and inflammation. The elevation of this marker in COVID-19 patients can be used as a predictive factor in the prognosis of these patients. Method Our cross-sectional study investigated the evaluation of cardiac diagnostic test findings based on pro-BNP levels in pregnant COVID-19 patients in Sayyad Shirazi Hospital, Gorgan, Iran, in 2020–2022. A hundred and ten pregnant patients diagnosed with COVID-19 infection were evaluated for cardiac diagnostic tests (electrocardiogram (ECG) and echocardiography (Echo)) and pro-BNP levels. Data were analyzed using SPSS 25 software. Chi-square and Student\'s t-test will be used to test and compare the relationship between variables and compare them. A P-value less than 0.05 is considered statistically significant. The chi-square test was used to compare the ratio of qualitative variables among the groups if the presuppositions of chi-square distribution were established. Otherwise, Fisher\'s exact test was used. Result The mean age of participants were 31.06 ± 5.533 years and 49.1% of patients had pro-BNP levels above the cut-off value for predicting an adverse outcome of COVID-19. The mean ± standard deviation of pro-BNP levels in the low group was 46.125 ± 17.523 pg/mL and in the high group was 878.814 ± 1038.060 pg/mL. This study revealed that patients with higher pro-BNP plasma levels had a significant relation between, myocardial infarction (MI), pericardial effusion (PE), urgent Caesarean section (C/S), and mortality. In addition, no significant relation between gravid, trimester, vaccination, arrhythmia, heart block, and valves diseases with high pro-BNP levels was found. Conclusion The current research showed that pro-BNP levels can be used as a diagnostic and valuable prognostic tool in pregnant women to diagnose cardiac complications by using ECG and Echo.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 13.11.2023
Tilføjet 13.11.2023
AbstractCD8 T cells recognize infected and cancerous cells via their T cell receptor (TCR), which binds peptide-MHC complexes on the target cell. The affinity of the interaction between the TCR and peptide-MHC contributes to the antigen sensitivity, or functional avidity, of the CD8 T cell. In response to peptide-MHC stimulation, the TCR-CD3 complex and CD8 co-receptor are downmodulated. We quantified CD3 and CD8 downmodulation following stimulation of human CD8 T cells with CMV, EBV, and HIV peptides spanning eight MHC restrictions, observing a strong correlation between the levels of CD3 and CD8 downmodulation and functional avidity, regardless of peptide viral origin. In TCR-transduced T cells targeting a tumor-associated antigen, changes in TCR-peptide affinity were sufficient to modify CD3 and CD8 downmodulation. Correlation analysis and generalized linear modelling indicated that CD3 downmodulation was the stronger correlate of avidity. CD3 downmodulation, simply measured using flow cytometry, can be used to identify high-avidity CD8 T cells in a clinical context.
Læs mere Tjek på PubMedInfection, 10.11.2023
Tilføjet 10.11.2023
Abstract Purpose The prevalence of odontogenic infections remains one of the highest in the world. If untreated, odontogenic infections can break through the limitation, disseminate to other organs or spaces, and cause high mortality rates. However, it is still difficult to rapidly target limited or disseminated infections in clinical practice. The type of disseminated odontogenic infections and the responsible bacteria have not been described in detail. Methods Search databases (e.g., PubMed, MEDLINE, Web of Science, Embase) for reports published from 2018.1 to 2022.9. Use search strategies: (“odontogenic infections” OR “pulpitis” OR “periapical lesions” OR “periodontal diseases”) AND (“disseminated infections” OR “complication”). Results Fourteen different types of disseminated odontogenic infections, most of which are polymicrobial infections, can spread through the body either direct or through hematogenous diffusion. Multiple microbial infections can be more invasive in the transmission of infection. Secondary infections are commonly associated with bacteria like Fusobacterium spp., Streptococcus spp., Peptostreptococcus spp., Prevotella spp., and Staphylococcus spp. Antibiotics with broad-spectrum activity are fundamental as first-line antimicrobial agents based on the microorganisms isolated from disseminated infections. Conclusion This review elaborates on the epidemiology, microorganisms, risk factors, and dissemination routes, and provides evidence-based opinions on the diagnosis, multidisciplinary management, and prevention of odontogenic infections for dentists and clinicians.
Læs mere Tjek på PubMedYan M. Crane, Charles F. Crane, Brandon J. Schemerhorn
PLoS One Infectious Diseases, 9.11.2023
Tilføjet 9.11.2023
by Yan M. Crane, Charles F. Crane, Brandon J. Schemerhorn An experiment was performed to measure the effect of Cereal Yellow-Dwarf Virus (CYDV), strain CYDV-RPV, on gene expression in its insect vector, greenbug aphid (Schizaphis graminum (Rondani)). RNA was sampled in three replicates from four treatments (biotypes B and H with or without carried CYDV), at 0, 1, 2, 3, 5, 10, 15 and 20 days from the introduction of carrier and virus-free greenbugs to uninfected wheat cv. ‘Newton’. Illumina paired-end sequencing produced 1,840,820,000,000 raw reads that yielded 1,089,950,000 clean reads, which were aligned to two greenbug, Trinity transcriptome assemblies with bowtie2. Read counts to contigs were analyzed with principal components and with DESeq2 after removing contaminating contigs of wheat or microbial origin. Likelihood ratio tests with one transcriptome showed that CYDV influenced gene expression about seven-fold less than time or biotype, which were approximately equal. With the other transcriptome, virus, time, and biotype were about equally important. Pairwise comparisons of virus to no virus for each timepoint yielded estimates of fold-change that comprised expression profiles for each contig when ordered by timepoint. Hierarchical clustering separated expression profiles into 20 groups of contigs that were significantly differentially expressed for at least one timepoint. Contigs were also sorted by timepoint of maximally differential expression between virus and no virus. All contigs that were significantly differentially expressed at FDR = 0.05 were annotated by blast searches against NCBI nr and nt databases. Interesting examples of up-regulation with virus included a lysosomal-trafficking regulator, peptidylprolylisomerase, RNA helicase, and two secreted effector proteins. However, carried virus did not consistently change aphid gene expression overall. Instead there was complex interaction of time, biotype, host response, and virus.
Læs mere Tjek på PubMedAmandine Pepiot, Virginie Supervie, Romulus Breban
PLoS One Infectious Diseases, 8.11.2023
Tilføjet 8.11.2023
by Amandine Pepiot, Virginie Supervie, Romulus Breban The World Health Organization recommends test-and-treat interventions to curb and even eliminate epidemics of HIV, viral hepatitis, and sexually transmitted infections (e.g., chlamydia, gonorrhea, syphilis and trichomoniasis). Epidemic models show these goals are achievable, provided the participation of individuals in test-and-treat interventions is sufficiently high. We combine epidemic models and game theoretic models to describe individual’s decisions to get tested for infectious diseases within certain epidemiological contexts, and, implicitly, their voluntary participation to test-and-treat interventions. We develop three hybrid models, to discuss interventions against HIV, HCV, and sexually transmitted infections, and the potential behavioral response from the target population. Our findings are similar across diseases. Particularly, individuals use three distinct behavioral patterns relative to testing, based on their perceived costs for testing, besides the payoff for discovering their disease status. Firstly, if the cost of testing is too high, then individuals refrain from voluntary testing and get tested only if they are symptomatic. Secondly, if the cost is moderate, some individuals will test voluntarily, starting treatment if needed. Hence, the spread of the disease declines and the disease epidemiology is mitigated. Thirdly, the most beneficial testing behavior takes place as individuals perceive a per-test payoff that surpasses a certain threshold, every time they get tested. Consequently, individuals achieve high voluntary testing rates, which may result in the elimination of the epidemic, albeit on temporary basis. Trials and studies have attained different levels of participation and testing rates. To increase testing rates, they should provide each eligible individual with a payoff, above a given threshold, each time the individual tests voluntarily.
Læs mere Tjek på PubMedInfection, 6.11.2023
Tilføjet 6.11.2023
Abstract Purpose The prevalence of odontogenic infections remains one of the highest in the world. If untreated, odontogenic infections can break through the limitation, disseminate to other organs or spaces, and cause high mortality rates. However, it is still difficult to rapidly target limited or disseminated infections in clinical practice. The type of disseminated odontogenic infections and the responsible bacteria have not been described in detail. Methods Search databases (e.g., PubMed, MEDLINE, Web of Science, Embase) for reports published from 2018.1 to 2022.9. Use search strategies: (“odontogenic infections” OR “pulpitis” OR “periapical lesions” OR “periodontal diseases”) AND (“disseminated infections” OR “complication”). Results Fourteen different types of disseminated odontogenic infections, most of which are polymicrobial infections, can spread through the body either direct or through hematogenous diffusion. Multiple microbial infections can be more invasive in the transmission of infection. Secondary infections are commonly associated with bacteria like Fusobacterium spp., Streptococcus spp., Peptostreptococcus spp., Prevotella spp., and Staphylococcus spp. Antibiotics with broad-spectrum activity are fundamental as first-line antimicrobial agents based on the microorganisms isolated from disseminated infections. Conclusion This review elaborates on the epidemiology, microorganisms, risk factors, and dissemination routes, and provides evidence-based opinions on the diagnosis, multidisciplinary management, and prevention of odontogenic infections for dentists and clinicians.
Læs mere Tjek på PubMedInfection, 5.11.2023
Tilføjet 5.11.2023
Abstract Background Antimicrobial stewardship (AMS) programs are effective tools for improving antibiotic prescription quality. Their implementation requires the regular surveillance of antibiotic consumption at the patient and institutional level. Our study captured and analyzed antibiotic consumption density (ACD) for hospitalized pediatric patients. Method We collected antibacterial drug consumption data for 2020 from hospital pharmacies at 113 pediatric departments of acute care hospitals in Germany. ACD was calculated as defined daily dose (DDD, WHO/ATC Index 2019) per 100 patient days (pd). In addition, we analyzed the trends in antibiotic use during 2013–2020. Results In 2020, median ACD across all participating hospitals was 26.7 DDD/100 pd, (range: 10.1–79.2 DDD/100 pd). It was higher at university vs. non-university hospitals (38.6 vs. 25.2 DDD/100 pd, p
Læs mere Tjek på PubMedClinical & Experimental Immunology, 5.11.2023
Tilføjet 5.11.2023
AbstractT cell engaging bispecifics have great clinical potential for the treatment of cancer and infectious diseases. The binding affinity and kinetics of a bispecific molecule for both target and T cell CD3 have substantial effects on potency and specificity, but the rules governing these relationships are not fully understood. Using ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules as a model, we explored the impact of altering affinity for target and CD3 on the potency and specificity of the re-directed T cell response. This class of bispecifics, exemplified by tebentafusp which has recently shown survival benefit in a randomized phase 3 clinical trial1, bind specific target peptides presented by human leukocyte antigen (HLA) on the cell surface via an affinity-enhanced T cell receptor and can redirect T cell activation with an anti-CD3 effector moiety. The data reveal that combining a strong affinity TCR with an intermediate affinity anti-CD3 results in optimal T cell activation, while strong affinity of both targeting and effector domains significantly reduces maximum cytokine release. Moreover, by optimising the affinity of both parts of the molecule, it is possible to improve the selectivity. These results could be effectively modelled based on kinetic proof-reading with limited signalling. This model explained the experimental observation that strong binding at both ends of the molecules leads to reduced activity, through very stable target-bispecific-effector complexes leading to CD3 entering a non-signalling dark-state. These findings have important implications for the design of anti-CD3 based bispecifics with optimal biophysical parameters for both activity and specificity.
Læs mere Tjek på PubMedM Suárez, A Pérez-Landeiro, A Sanjurjo, O. Lima, A. Sousa, A. López, L. Martínez-Lamas, X. Cabrera, M Rubianes, MT Pérez-Rodríguez
International Journal of Infectious Diseases, 4.11.2023
Tilføjet 4.11.2023
Dalbavancin is a lipoglycopeptide antibiotic that has a lipophilic side chain that gives it a long half-life, allowing weekly or every two weeks administration [1–3]. It has been approved for the treatment of skin and soft tissue infections [2]. Its innovative posology could offer great advantages in the consolidation treatment of infections that require prolonged antibiotic treatment, such as infective endocarditis (IE), and osteoarticular infection [3–5].
Læs mere Tjek på PubMedInfection, 2.11.2023
Tilføjet 2.11.2023
Abstract Background Antimicrobial stewardship (AMS) programs are effective tools for improving antibiotic prescription quality. Their implementation requires the regular surveillance of antibiotic consumption at the patient and institutional level. Our study captured and analyzed antibiotic consumption density (ACD) for hospitalized pediatric patients. Method We collected antibacterial drug consumption data for 2020 from hospital pharmacies at 113 pediatric departments of acute care hospitals in Germany. ACD was calculated as defined daily dose (DDD, WHO/ATC Index 2019) per 100 patient days (pd). In addition, we analyzed the trends in antibiotic use during 2013–2020. Results In 2020, median ACD across all participating hospitals was 26.7 DDD/100 pd, (range: 10.1–79.2 DDD/100 pd). It was higher at university vs. non-university hospitals (38.6 vs. 25.2 DDD/100 pd, p
Læs mere Tjek på PubMedBrent W. SimpsonMichael C. GilmoreAmanda Briann McLeanFelipe CavaM. Stephen TrentaDepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602bLaboratory for Molecular Infection Medicine Sweden, Umeå Center for Microbial Research, Department of Molecular Biology, Umeå University, Umeå 90187, SwedencDepartment of Microbiology, College of Art and Sciences, University of Georgia, Athens, GA 30602
Proceedings of the National Academy of Sciences, 2.11.2023
Tilføjet 2.11.2023
Proceedings of the National Academy of Sciences, Volume 120, Issue 44, October 2023.
Læs mere Tjek på PubMedProceedings of the National Academy of Sciences, 2.11.2023
Tilføjet 2.11.2023
Proceedings of the National Academy of Sciences, Volume 120, Issue 44, October 2023.
Læs mere Tjek på PubMedShanjana AwasthiBhupinder SinghVijay RamaniNachiket M. GodboleCatherine King 1 Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA , Kimberly A. Kline
Infection and Immunity, 1.11.2023
Tilføjet 1.11.2023
Lai, Mason; Madden, Erin; Shlipak, Michael G.; Scherzer, Rebecca; Post, Wendy S.; Vittinghoff, Eric; Haberlen, Sabina; Brown, Todd T.; Wolinsky, Steven M.; Witt, Mallory D.; Ho, Ken; Abraham, Alison G.; Parikh, Chirag R.; Budoff, Matthew; Estrella, Michelle M.
AIDS, 28.10.2023
Tilføjet 28.10.2023
Objective: To determine whether urine biomarkers of kidney health are associated with subclinical cardiovascular disease among men living with and without HIV. Design: Cross-sectional study within the Multicenter AIDS Cohort Study (MACS) among 504 men with and without HIV infection who underwent cardiac computed tomography scans and had urine biomarkers measured within the preceding two years. Methods: Our primary predictors were four urine biomarkers of endothelial (albuminuria), proximal tubule dysfunction (alpha-1-microglobulin [A1 M] and injury (kidney injury molecule-1 [KIM-1]) and tubulointerstitial fibrosis (pro-collagen-III N-terminal peptide [PIIINP]). These were evaluated for association with coronary artery calcium (CAC) prevalence, CAC extent, total plaque score, and total segment stenosis using multivariable regression. Results: Of the 504 participants, 384 were men with HIV (MWH) and 120 were men without HIV. In models adjusted for sociodemographic factors, cardiovascular disease risk factors, eGFR, and HIV-related factors, each two-fold higher concentration of albuminuria was associated with a greater extent of CAC (1.35-fold higher, 95% CI [1.11, 1.65]), and segment stenosis (1.08-fold greater, 95% CI [1.01, 1.16]). Associations were similar between MWH and men without HIV in stratified analyses. The third quartile of A1 M showed an association with greater CAC extent, total plaque score, and total segment stenosis, compared with the lowest quartile. Conclusions: Worse endothelial and proximal tubule dysfunction as reflected by higher urine albumin and A1 M, were associated with greater CAC extent and coronary artery stenosis. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedKoss, Catherine A.; Ayieko, James; Kabami, Jane; Balzer, Laura B.; Kakande, Elijah; Sunday, Helen; Nyabuti, Marilyn; Wafula, Erick; Shade, Starley; Biira, Edith; Opel, Fred; Atuhaire, Hellen N.; Okochi, Hideaki; Ogachi, Sabina; Gandhi, Monica; Bacon, Melanie C.; Bukusi, Elizabeth A.; Chamie, Gabriel; Petersen, Maya L.; Kamya, Moses R.; Havlir, Diane V.
AIDS, 28.10.2023
Tilføjet 28.10.2023
Objective: HIV prevention service delivery models that offer product choices, and the option to change preferences over time, may increase prevention coverage. Outpatient departments in sub-Saharan Africa diagnose a high proportion of new HIV infections, but are an understudied entry point to biomedical prevention. Design: Individually randomized trial of dynamic choice HIV prevention (DCP) intervention vs. standard-of-care (SOC) among individuals with current/anticipated HIV exposure risk at outpatient departments in rural Kenya and Uganda (SEARCH; NCT04810650). Methods: Our DCP intervention included 1) product choice (oral pre-exposure prophylaxis [PrEP] or post-exposure prophylaxis [PEP]) with option to switch over time, 2) HIV provider- or self-testing, 3) service location choice (community vs. clinic-based), 4) provider training on patient-centered care. Primary outcome was proportion of follow-up covered by PrEP/PEP over 48 weeks assessed via self-report. Results: We enrolled 403 participants (61% women; median 27 years, IQR 22,37). In the DCP arm, 86% ever chose PrEP, 15% ever chose PEP over 48 weeks; selection of HIV self-testing increased from 26% to 51% and of out-of-facility visits from 8% to 52%. Among 376/403 (93%) with outcomes ascertained, time covered by PrEP/PEP was higher in DCP (47.5%) vs. SOC (18.3%); difference=29.2% (95%CI:22.7–35.7%; p
Læs mere Tjek på PubMedNatsuki WatanabeYumiko Saito-NakanoNaoaki KurisawaKeisuke OtomoKiyotake SuenagaKentaro NakanoTomoyoshi Nozaki1Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan2Department of Parasitology and Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan3Department of Chemistry, Faculty of Science and Technology, Keio University, Kanagawa, Japan4Degree Programs in Biology, Graduate School of Science and Technology, University of Tsukuba, Ibaraki, Japan, Audrey Odom John
Antimicrobial Agents And Chemotherapy, 24.10.2023
Tilføjet 24.10.2023