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Søgeord (pep) valgt.
62 emner vises.
Weiyi Tan, Hai Nian, Lam-Son Phan Tran, Jing Jin, Tengxiang Lian
Trends in Microbiology, 26.04.2024
Tilføjet 26.04.2024
The crucial role of rhizosphere microbes in plant growth and their resilience to environmental stresses underscores the intricate communication between microbes and plants. Plants are equipped with a diverse set of signaling molecules that facilitate communication across different biological kingdoms, although our comprehension of these mechanisms is still evolving. Small peptides produced by plants (SPPs) and microbes (SPMs) play a pivotal role in intracellular signaling and are essential in orchestrating various plant development stages. In this review, we posit that SPPs and SPMs serve as crucial signaling agents for the bidirectional cross-kingdom communication between plants and rhizosphere microbes. We explore several potential mechanistic pathways through which this communication occurs. Additionally, we propose that leveraging small peptides, inspired by plant–rhizosphere microbe interactions, represents an innovative approach in the field of holobiont engineering.
Læs mere Tjek på PubMedBMC Infectious Diseases, 25.04.2024
Tilføjet 25.04.2024
Abstract Background In recent years, the prevalence of respiratory fungal diseases has increased. Polyene antifungal drugs play a pivotal role in the treatment of these conditions, with amphotericin B (AmB) being the most representative drug. This study aimed to evaluate the efficacy and safety of topical administration of AmB in the treatment of respiratory fungal infections. Methods We conducted a retrospective study on hospitalized patients treated with topical administered AmB for respiratory fungal infections from January 2014 to June 2023. Results Data from 36 patients with invasive pulmonary fungal infections treated with topical administration of AmB were collected and analyzed. Nebulization was administered to 27 patients. After the treatment, 17 patients evidenced improved conditions, whereas 10 patients did not respond and died in the hospital. One patient experienced an irritating cough as an adverse reaction. Seven patients underwent tracheoscopic instillation, and two received intrapleural irrigation; they achieved good clinical therapeutic efficacy without adverse effects. Conclusion The combined application of systemic antifungal treatment and topical administration of AmB yielded good therapeutic efficacy and was well-tolerated by the patients. Close monitoring of routine blood tests, liver and kidney function, and levels of electrolytes, troponin, and B-type natriuretic peptide supported this conclusion.
Læs mere Tjek på PubMedClinical Infectious Diseases, 24.04.2024
Tilføjet 24.04.2024
Hadil Alahdal, Ghaida Almuneef, Manal Muhammed Alkhulaifi, Omar Aldibasi, Abdulrahman Aljouie, Othman Alharbi, Zakiah Naser Almohawes, Fatemah Basingab, Mokhtar Rejili
PLoS One Infectious Diseases, 24.04.2024
Tilføjet 24.04.2024
by Hadil Alahdal, Ghaida Almuneef, Manal Muhammed Alkhulaifi, Omar Aldibasi, Abdulrahman Aljouie, Othman Alharbi, Zakiah Naser Almohawes, Fatemah Basingab, Mokhtar Rejili Crohn’s disease (CD) entails intricate interactions with gut microbiome diversity, richness, and composition. The relationship between CD and gut microbiome is not clearly understood and has not been previously characterized in Saudi Arabia. We performed statistical analysis about various factors influencing CD activity and microbiota dysbiosis, including diagnosis, treatment, and its impact on their quality of life as well as high-throughput metagenomic V3-V4 16S rRNA encoding gene hypervariable region of a total of eighty patients with CD, both in its active and inactive state with healthy controls. The results were correlated with the demographic and lifestyle information, which the participants provided via a questionnaire. α-diversity measures indicated lower bacterial diversity and richness in the active and inactive CD groups compared to the control group. Greater dysbiosis was observed in the active CD patients compared to the inactive form of the disease, showed by a reduction in microbial diversity. Specific pathogenic bacteria such as Filifactor, Peptoniphilus, and Sellimonas were identified as characteristic of CD groups. In contrast, anti-inflammatory bacteria like Defluviitalea, Papillibacter, and Petroclostridium were associated with the control group. Among the various factors influencing disease activity and microbiota dysbiosis, smoking emerged as the most significant, with reduced α-diversity and richness for the smokers in all groups, and proinflammatory Fusobacteria was more present (p
Læs mere Tjek på PubMedSano, M., Toyota, T., Morimoto, T., Noguchi, Y., Shigeno, R., Murai, R., Okada, T., Sasaki, Y., Taniguchi, T., Kim, K., Kobori, A., Ehara, N., Kinoshita, M., Doi, A., Tomii, K., Kihara, Y., Furukawa, Y.
BMJ Open, 24.04.2024
Tilføjet 24.04.2024
ObjectiveThere is a need for a robust tool to stratify the patient’s risk with COVID-19. We assessed the prognostic values of cardiac biomarkers for COVID-19 patients. MethodsThis is a single-centre retrospective cohort study. Consecutive laboratory-confirmed COVID-19 patients admitted to the Kobe City Medical Center General Hospital from July 2020 to September 2021 were included. We obtained cardiac biomarker values from electronic health records and institutional blood banks. We stratified patients with cardiac biomarkers as high-sensitive troponin I (hsTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase (CK) and CK myocardial band (CK-MB), using the clinically relevant thresholds. Prespecified primary outcome measure was all-cause death. ResultsA total of 917 patients were included. hsTnI, NT-proBNP, CK and CK-MB were associated with the significantly higher cumulative 30-day incidence of all-cause death (hsTnI:
Læs mere Tjek på PubMedPaige K. Marty, Balaji Pathakumari, Thomas M. Cox, Virginia P. Van Keulen, Courtney L. Erskine, Maleeha Shah, Mounika Vadiyala, Pedro Arias-Sanchez, Snigdha Karnakoti, Kelly M. Pennington, Elitza S. Theel, Cecilia S. Lindestam Arlehamn, Tobias Peikert, Patricio Escalante
PLoS One Infectious Diseases, 20.04.2024
Tilføjet 20.04.2024
by Paige K. Marty, Balaji Pathakumari, Thomas M. Cox, Virginia P. Van Keulen, Courtney L. Erskine, Maleeha Shah, Mounika Vadiyala, Pedro Arias-Sanchez, Snigdha Karnakoti, Kelly M. Pennington, Elitza S. Theel, Cecilia S. Lindestam Arlehamn, Tobias Peikert, Patricio Escalante Clinical prediction of nontuberculous mycobacteria lung disease (NTM-LD) progression remains challenging. We aimed to evaluate antigen-specific immunoprofiling utilizing flow cytometry (FC) of activation-induced markers (AIM) and IFN-γ enzyme-linked immune absorbent spot assay (ELISpot) accurately identifies patients with NTM-LD, and differentiate those with progressive from nonprogressive NTM-LD. A Prospective, single-center, and laboratory technician-blinded pilot study was conducted to evaluate the FC and ELISpot based immunoprofiling in patients with NTM-LD (n = 18) and controls (n = 22). Among 18 NTM-LD patients, 10 NTM-LD patients were classified into nonprogressive, and 8 as progressive NTM-LD based on clinical and radiological features. Peripheral blood mononuclear cells were collected from patients with NTM-LD and control subjects with negative QuantiFERON results. After stimulation with purified protein derivative (PPD), mycobacteria-specific peptide pools (MTB300, RD1-peptides), and control antigens, we performed IFN-γ ELISpot and FC AIM assays to access their diagnostic accuracies by receiver operating curve (ROC) analysis across study groups. Patients with NTM-LD had significantly higher percentage of CD4+/CD8+ T-cells co-expressing CD25+CD134+ in response to PPD stimulation, differentiating between NTM-LD and controls. Among patients with NTM-LD, there was a significant difference in CD25+CD134+ co-expression in MTB300-stimulated CD8+ T-cells (p
Læs mere Tjek på PubMedInternational Journal for Parasitology, 16.04.2024
Tilføjet 16.04.2024
Publication date: Available online 16 April 2024 Source: International Journal for Parasitology Author(s): Barbora Vomáčková Kykalová, Fabiana Sassù, Felipe Dutra Rêgo, Rodrigo Pedro Soares, Petr Volf, Erich Loza Telleria
Læs mere Tjek på PubMedJuan F. Zapata-Acevedo, Mónica Losada-Barragán, Johann F. Osma, Juan C. Cruz, Andreas Reiber, Klaus G. Petry, Amael Caillard, Audrey Sauldubois, Daniel Llamosa Pérez, Aníbal José Morillo Zárate, Sonia Bermúdez Muñoz, Agustín Daza Moreno, Rafaela V. Silva, Carmen Infante-Duarte, William Chamorro-Coral, Rodrigo E. González-Reyes, Karina Vargas-Sánchez
PLoS One Infectious Diseases, 12.04.2024
Tilføjet 12.04.2024
by Juan F. Zapata-Acevedo, Mónica Losada-Barragán, Johann F. Osma, Juan C. Cruz, Andreas Reiber, Klaus G. Petry, Amael Caillard, Audrey Sauldubois, Daniel Llamosa Pérez, Aníbal José Morillo Zárate, Sonia Bermúdez Muñoz, Agustín Daza Moreno, Rafaela V. Silva, Carmen Infante-Duarte, William Chamorro-Coral, Rodrigo E. González-Reyes, Karina Vargas-Sánchez Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1β (IL-1β) for 3 and 24 hours. IL-1β for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.
Læs mere Tjek på PubMedGuoguo Ye, Yimin Tang, Qin Yang, Chenhui Zhang, Huiping Shi, Jun Wang, Xiao Hu, Xiaofu Wan, Zhixiang Xu, Jinhu Liang, Yang Yang, Minghui Yang, Yingxia Liu
Journal of Medical Virology, 9.04.2024
Tilføjet 9.04.2024
Journal of Infectious Diseases, 7.04.2024
Tilføjet 7.04.2024
Abstract Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized three gene operon (madEFG) that protects the E. faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of a functional LiaFSR system and leads to persistence of cardiac microlesions in vivo. Moreover, changes in the lipid cell membrane environment alter CAMP susceptibility and expression of the MadRS system. Thus, we provide a framework supporting a multilayered envelope defense mechanism for resistance and survival coupled to virulence.
Læs mere Tjek på PubMedBMC Infectious Diseases, 6.04.2024
Tilføjet 6.04.2024
Abstract There is considerable interest in the use of doxycycline post exposure prophylaxis (PEP) to reduce the incidence of bacterial sexually transmitted infections (STIs). An important concern is that this could select for tetracycline resistance in these STIs and other species. We searched PubMed and Google Scholar, (1948–2023) for randomized controlled trials comparing tetracycline PEP with non-tetracycline controls. The primary outcome was antimicrobial resistance (AMR) to tetracyclines in all bacterial species with available data. Our search yielded 140 studies, of which three met the inclusion criteria. Tetracycline PEP was associated with an increasedprevalence of tetracycline resistance in Neisseria gonorrhoeae, but this effect was not statistically significant (Pooled OR 2.3, 95% CI 0.9-3.4). PEP had a marked effect on the N. gonorrhoeae tetracycline MIC distribution in the one study where this was assessed. Prophylactic efficacy was 100% at low MICs and 0% at high MICs. In the one study where this was assessed, PEP resulted in a significant increase in tetracycline resistance in commensal Neisseria species compared to the control group (OR 2.9, 95% CI 1.5-5.5) but no significant effect on the prevalence of tetracycline resistance in Staphylococcus aureus. The available evidence suggests that PEP with tetracyclines could be associated with selecting tetracycline resistance in N. gonorrhoeae and commensal Neisseria species.
Læs mere Tjek på PubMedPhilippe Maury, Kevin Sanchis, Kamila Djouadi, Eve Cariou, Hubert Delasnerie, Serge Boveda, Pauline Fournier, Romain Itier, Pierre Mondoly, Quentin Voglimacci-Stephanopoli, Maxime Beneyto, Tarvinder S. Dhanjal, Anne Rollin, Thibaud Damy, Olivier Lairez, Nicolas Lellouche
PLoS One Infectious Diseases, 5.04.2024
Tilføjet 5.04.2024
by Philippe Maury, Kevin Sanchis, Kamila Djouadi, Eve Cariou, Hubert Delasnerie, Serge Boveda, Pauline Fournier, Romain Itier, Pierre Mondoly, Quentin Voglimacci-Stephanopoli, Maxime Beneyto, Tarvinder S. Dhanjal, Anne Rollin, Thibaud Damy, Olivier Lairez, Nicolas Lellouche Background Atrial arrhythmias (AA) commonly affect patients with cardiac amyloidosis (CA) and are a contributing risk factor for the development of heart failure (HF). This study sought to investigate the long-term efficacy and impact of catheter ablation on HF progression in patients with CA and AA. Methods Thirty-one patients with CA and AA undergoing catheter ablation were retrospectively included (transthyretin—ATTR CA 61% and light chain—AL CA 39%). AA subtypes included atrial fibrillation (AFib) in 22 (paroxysmal in 10 and persistent in 12), atrial flutter (AFl) in 17 and atrial tachycardia (AT) in 11 patients. Long-term AA recurrence rates were evaluated along with the impact of sinus rhythm (SR) maintenance on HF and mortality. Results AA recurrence was observed in 14 patients (45%) at a median of 3.5 months (AFib n = 8, AT n = 6, AFl = 0). Post-cardioversion, medical therapy or catheter ablation, 10 patients (32%) remained in permanent AA. Over a median follow-up of 19 months, all-cause mortality was 39% (n = 12): 3 with end-stage HF, 5 due to late complications of CA, 1 sudden cardiac death, 1 stroke, 1 COVID 19 (and one unknown). With maintenance of SR following catheter ablation, significant reductions in serum creatinine and natriuretic peptide levels were observed with improvements in NYHA class. Two patients required hospitalization for HF in the SR maintenance cohort compared to 5 patients in the AA recurrence cohort (p = 0.1). All 3 patients with deaths secondary to HF had AA recurrence compared to 11 out of the 28 patients whom were long-term survivors or deaths not related to HF (p = 0.04). All-cause mortality was not associated with AA recurrence. Conclusion This study demonstrates moderate long-term efficacy of SR maintenance with catheter ablation for AA in patients with CA. Improvements in clinical and biological status with positive trends in HF mortality are observed if SR can be maintained.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 5.04.2024
Tilføjet 5.04.2024
BMC Infectious Diseases, 5.04.2024
Tilføjet 5.04.2024
Abstract There is considerable interest in the use of doxycycline post exposure prophylaxis (PEP) to reduce the incidence of bacterial sexually transmitted infections (STIs). An important concern is that this could select for tetracycline resistance in these STIs and other species. We searched PubMed and Google Scholar, (1948–2023) for randomized controlled trials comparing tetracycline PEP with non-tetracycline controls. The primary outcome was antimicrobial resistance (AMR) to tetracyclines in all bacterial species with available data. Our search yielded 140 studies, of which three met the inclusion criteria. Tetracycline PEP was associated with an increasedprevalence of tetracycline resistance in Neisseria gonorrhoeae, but this effect was not statistically significant (Pooled OR 2.3, 95% CI 0.9-3.4). PEP had a marked effect on the N. gonorrhoeae tetracycline MIC distribution in the one study where this was assessed. Prophylactic efficacy was 100% at low MICs and 0% at high MICs. In the one study where this was assessed, PEP resulted in a significant increase in tetracycline resistance in commensal Neisseria species compared to the control group (OR 2.9, 95% CI 1.5-5.5) but no significant effect on the prevalence of tetracycline resistance in Staphylococcus aureus. The available evidence suggests that PEP with tetracyclines could be associated with selecting tetracycline resistance in N. gonorrhoeae and commensal Neisseria species.
Læs mere Tjek på PubMedChipepo Kankasa, Anaïs Mennecier, Beninwendé L D Sakana, Jean-Pierre Molès, Mwiya Mwiya, Catherine Chunda-Liyoka, Morgana D'Ottavi, Souleymane Tassembedo, Maria M Wilfred-Tonga, Paulin Fao, David Rutagwera, Beauty Matoka, Dramane Kania, Ousmane A Taofiki, Thorkild Tylleskär, Philippe Van de Perre, Nicolas Nagot, PROMISE-EPI Trial Group
Lancet, 5.04.2024
Tilføjet 5.04.2024
Our intervention, initiated at EPI-2 and based on extended single-drug postnatal prophylaxis guided by point-of-care maternal viral load could be an important strategy for paediatric HIV elimination.
Læs mere Tjek på PubMedWinston T. Stauffer, Michael Bobardt, Daren R. Ure, Robert T. Foster, Philippe Gallay
PLoS One Infectious Diseases, 4.04.2024
Tilføjet 4.04.2024
by Winston T. Stauffer, Michael Bobardt, Daren R. Ure, Robert T. Foster, Philippe Gallay A family of Peptidyl-prolyl isomerases (PPIases), called Cyclophilins, localize to numerous intracellular and extracellular locations where they contribute to a variety of essential functions. We previously reported that non-immunosuppressive pan-cyclophilin inhibitor drugs like reconfilstat (CRV431) or NV556 decreased multiple aspects of non-alcoholic fatty liver disease (NAFLD) in mice under two different non-alcoholic steatohepatitis (NASH) mouse models. Both CRV431 and NV556 inhibit several cyclophilin isoforms, among which cyclophilin D (CypD) has not been previously investigated in this context. It is unknown whether it is necessary to simultaneously inhibit multiple cyclophilin family members to achieve therapeutic benefits or if loss-of-function of one is sufficient. Furthermore, narrowing down the isoform most responsible for a particular aspect of NAFLD/NASH, such as hepatocellular carcinoma (HCC), would allow for more precise future therapies. Features of human diabetes-linked NAFLD/NASH can be reliably replicated in mice by administering a single high dose of streptozotocin to disrupt pancreatic beta cells, in conjunction with a high sugar, high fat, high cholesterol western diet over the course of 30 weeks. Here we show that while both wild-type (WT) and Ppif-/- CypD KO mice develop multipe severe NASH disease features under this model, the formation of HCC nodules was significantly blunted only in the CypD KO mice. Furthermore, of differentially expressed transcripts in a qPCR panel of select HCC-related genes, nearly all were downregulated in the CypD KO background. Cyclophilin inhibition is a promising and novel avenue of treatment for diet-induced NAFLD/NASH. This study highlights the impact of CypD loss-of-function on the development of HCC, one of the most severe disease outcomes.
Læs mere Tjek på PubMedBMC Infectious Diseases, 4.04.2024
Tilføjet 4.04.2024
Abstract Background There is an urgent clinical need for developing novel immunoprophylaxis and immunotherapy strategies against Staphylococcus aureus (S. aureus). In our previous work, immunization with a tetra-branched multiple antigenic peptide, named MAP2-3 that mimics lipoteichoic acid, a cell wall component of S. aureus, successfully induced a humoral immune response and protected BALB/c mice against S. aureus systemic infection. In this study, we further investigated whether vaccination with MAP2-3 can elicit immunologic memory. Methods BALB/c mice were immunized with MAP2-3 five times. After one month of the last vaccination, mice were challenged with heat-killed S. aureus via intraperitoneal injection. After a 7-day inoculation, the percentage of plasma cells, memory B cells, effector memory T cells, and follicular helper T cells were detected by flow cytometry. The levels of IL-6, IL-21, IL-2, and IFN-γ were measured by real-time PCR and ELISA. Flow cytometry results were compared by using one-way ANOVA or Mann-Whitney test, real-time PCR results were compared by using one-way ANOVA, and ELISA results were compared by using one-way ANOVA or student’s t-test. Results The percentage of plasma cells and memory B cells in the spleen and bone marrow from the MAP2-3 immunized mice was significantly higher than that from the control mice. The percentage of effector memory T cells in spleens and lymphoid nodes as well as follicular helper T cells in spleens from the MAP2-3 immunized mice were also higher. Moreover, the levels of IL-6 and IL-21, two critical cytokines for the development of memory B cells, were significantly higher in the isolated splenocytes from immunized mice after lipoteichoic acid stimulation. Conclusions Immunization with MAP2-3 can efficiently induce memory B cells and memory T cells.
Læs mere Tjek på PubMedBMC Infectious Diseases, 3.04.2024
Tilføjet 3.04.2024
Abstract Background There is an urgent clinical need for developing novel immunoprophylaxis and immunotherapy strategies against Staphylococcus aureus (S. aureus). In our previous work, immunization with a tetra-branched multiple antigenic peptide, named MAP2-3 that mimics lipoteichoic acid, a cell wall component of S. aureus, successfully induced a humoral immune response and protected BALB/c mice against S. aureus systemic infection. In this study, we further investigated whether vaccination with MAP2-3 can elicit immunologic memory. Methods BALB/c mice were immunized with MAP2-3 five times. After one month of the last vaccination, mice were challenged with heat-killed S. aureus via intraperitoneal injection. After a 7-day inoculation, the percentage of plasma cells, memory B cells, effector memory T cells, and follicular helper T cells were detected by flow cytometry. The levels of IL-6, IL-21, IL-2, and IFN-γ were measured by real-time PCR and ELISA. Flow cytometry results were compared by using one-way ANOVA or Mann-Whitney test, real-time PCR results were compared by using one-way ANOVA, and ELISA results were compared by using one-way ANOVA or student’s t-test. Results The percentage of plasma cells and memory B cells in the spleen and bone marrow from the MAP2-3 immunized mice was significantly higher than that from the control mice. The percentage of effector memory T cells in spleens and lymphoid nodes as well as follicular helper T cells in spleens from the MAP2-3 immunized mice were also higher. Moreover, the levels of IL-6 and IL-21, two critical cytokines for the development of memory B cells, were significantly higher in the isolated splenocytes from immunized mice after lipoteichoic acid stimulation. Conclusions Immunization with MAP2-3 can efficiently induce memory B cells and memory T cells.
Læs mere Tjek på PubMedTomomi Sawabe, Yoshihiro Ojima, Mao Nakagawa, Toru Sawada, Yuhei O. Tahara, Makoto Miyata, Masayuki Azuma
PLoS One Infectious Diseases, 3.04.2024
Tilføjet 3.04.2024
by Tomomi Sawabe, Yoshihiro Ojima, Mao Nakagawa, Toru Sawada, Yuhei O. Tahara, Makoto Miyata, Masayuki Azuma Outer membrane vesicles (OMVs) are produced by Gram-negative bacteria and deliver microbial molecules to distant target cells in a host. OMVs secreted by probiotic probiotic strain Escherichia coli Nissle 1917 (EcN) have been reported to induce an immune response. In this study, we aimed to increase the OMV production of EcN. The double gene knockout of mlaE and nlpI was conducted in EcN because the ΔmlaEΔnlpI of experimental strain E. coli K12 showed the highest OMV production in our previous report. The ΔmlaEΔnlpI of EcN showed approximately 8 times higher OMV production compared with the parental (wild-type) strain. Quick-freeze, deep-etch replica electron microscopy revealed that plasmolysis occurred in the elongated ΔmlaEΔnlpI cells and the peptidoglycan (PG) had numerous holes. While these phenomena are similar to the findings for the ΔmlaEΔnlpI of K12, there were more PG holes in the ΔmlaEΔnlpI of EcN than the K12 strain, which were observed not only at the tip of the long axis but also in the whole PG structure. Further analysis clarified that the viability of ΔmlaEΔnlpI of EcN decreased compared with that of the wild-type. Although the amount of PG in ΔmlaEΔnlpI cells was about half of that in wild-type, the components of amino acids in PG did not change in ΔmlaEΔnlpI. Although the viability decreased compared to the wild-type, the ΔmlaEΔnlpI grew in normal culture conditions. The hypervesiculation strain constructed here is expected to be used as an enhanced probiotic strain.
Læs mere Tjek på PubMedTiffany N. Harris-JonesJia Mun ChanKathleen T. HackettNathan J. WeyandRyan E. SchaubJoseph P. Dillard1Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA2Department of Biological Sciences, Ohio University, Athens, Ohio, USA, Kimberly A. Kline
Infection and Immunity, 3.04.2024
Tilføjet 3.04.2024
Journal of Infectious Diseases, 28.03.2024
Tilføjet 28.03.2024
Abstract Concerns regarding toxicity and resistance of current drugs have been reported in visceral leishmaniasis. Anti-microbial peptides are considered as new promising candidates and amongst them, human cathelicidin hCAP18/LL-37 showed significant parasite killing on drug-sensitive and resistant Leishmania promastigotes, coupled with its apoptosis-inducing role. Administration of hCAP18/LL-37 in infected macrophages also decreased parasite survival and increased the host favorable cytokine IL-12. However, 1,25-dihydroxyvitamin D3 (VitD3)-induced endogenous hCAP18/LL-37 production was hampered in infected THP-1 cells. Infection also suppressed the VitD3-receptor (VDR), transcription factor of hCAP18/LL-37. cAMP response element modulator (CREM), the repressor of VDR, was induced in infection resulting in suppression of both VDR and cathelicidin expression. PGE2/cAMP/PKA axis was found to regulate CREM induction during infection and silencing CREM in infected cells and BALB/c mice led to decreased parasite survival. Present study thus documents the anti-leishmanial potential of cathelicidin and further identifies CREM as a repressor of cathelicidin in Leishmania infection.
Læs mere Tjek på PubMedTulika Munshi, Antima Gupta, Dimitrios Evangelopoulos, Juan David Guzman, Simon Gibbons, Nicholas H. Keep, Sanjib Bhakta
PLoS One Infectious Diseases, 27.03.2024
Tilføjet 27.03.2024
by Tulika Munshi, Antima Gupta, Dimitrios Evangelopoulos, Juan David Guzman, Simon Gibbons, Nicholas H. Keep, Sanjib Bhakta
Læs mere Tjek på PubMedCrowell, Trevor A.; Ritz, Justin; Zheng, Lu; Naqvi, Asma; Cyktor, Joshua C.; Puleo, Joseph; Clagett, Brian; Lama, Javier R.; Kanyama, Cecilia; Little, Susan J.; Cohn, Susan E.; Riddler, Sharon A.; Collier, Ann C.; Heath, Sonya L.; Tantivitayakul, Pornphen; Grinsztejn, Beatriz; Arduino, Roberto C.; Rooney, James F.; van Zyl, Gert U.; Coombs, Robert W.; Fox, Lawrence; Ananworanich, Jintanat; Eron, Joseph J.; Sieg, Scott F.; Mellors, John W.; Daar, Eric S.; for the AIDS Clinical Trials Group (ACTG) A5354/EARLIER Study Team
AIDS, 23.03.2024
Tilføjet 23.03.2024
Objective: To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses. Design: Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia. Methods: HIV DNA was measured at week 48 of ART in 5 million CD4+ T cells by sensitive qPCR assays targeting HIV gag and pol. Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env, gag, nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines. Results: From 2017 to 2019, 188 participants initiated ART during Fiebig stages I (n = 6), II (n = 43), III (n = 56), IV (n = 23), and V (n = 60). Median age was 27 years (interquartile range 23–38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels (P 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest. Conclusion: Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedGrzegorz Dudek, Sebastian Sakowski, Olga Brzezińska, Joanna Sarnik, Tomasz Budlewski, Grzegorz Dragan, Marta Poplawska, Tomasz Poplawski, Michał Bijak, Joanna Makowska
PLoS One Infectious Diseases, 22.03.2024
Tilføjet 22.03.2024
by Grzegorz Dudek, Sebastian Sakowski, Olga Brzezińska, Joanna Sarnik, Tomasz Budlewski, Grzegorz Dragan, Marta Poplawska, Tomasz Poplawski, Michał Bijak, Joanna Makowska Machine learning (ML) algorithms can handle complex genomic data and identify predictive patterns that may not be apparent through traditional statistical methods. They become popular tools for medical applications including prediction, diagnosis or treatment of complex diseases like rheumatoid arthritis (RA). RA is an autoimmune disease in which genetic factors play a major role. Among the most important genetic factors predisposing to the development of this disease and serving as genetic markers are HLA-DRB and non-HLA genes single nucleotide polymorphisms (SNPs). Another marker of RA is the presence of anticitrullinated peptide antibodies (ACPA) which is correlated with severity of RA. We use genetic data of SNPs in four non-HLA genes (PTPN22, STAT4, TRAF1, CD40 and PADI4) to predict the occurrence of ACPA positive RA in the Polish population. This work is a comprehensive comparative analysis, wherein we assess and juxtapose various ML classifiers. Our evaluation encompasses a range of models, including logistic regression, k-nearest neighbors, naïve Bayes, decision tree, boosted trees, multilayer perceptron, and support vector machines. The top-performing models demonstrated closely matched levels of accuracy, each distinguished by its particular strengths. Among these, we highly recommend the use of a decision tree as the foremost choice, given its exceptional performance and interpretability. The sensitivity and specificity of the ML models is about 70% that are satisfying. In addition, we introduce a novel feature importance estimation method characterized by its transparent interpretability and global optimality. This method allows us to thoroughly explore all conceivable combinations of polymorphisms, enabling us to pinpoint those possessing the highest predictive power. Taken together, these findings suggest that non-HLA SNPs allow to determine the group of individuals more prone to develop RA rheumatoid arthritis and further implement more precise preventive approach.
Læs mere Tjek på PubMedIsabel M. BarcelóMaria Escobar-SalomGabriel CabotPau Perelló-BauzàElena Jordana-LluchBiel TaltavullGabriel TorrensEstrella Rojo-MolineroLaura ZamoranoAstrid PérezAntonio OliverCarlos Juan1Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain2Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain3Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain4Department of Molecular Biology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden5National Center for Microbiology, Instituto de Salud Carlos III (ISCIII), Madrid, Spain, Laurent Poirel
Antimicrobial Agents And Chemotherapy, 22.03.2024
Tilføjet 22.03.2024
Clinical Infectious Diseases, 21.03.2024
Tilføjet 21.03.2024
Clinical Infectious Diseases, 21.03.2024
Tilføjet 21.03.2024
Abstract Background Weight gain and associated metabolic complications are increasingly prevalent among people with HIV (PWH). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin-based therapies for diabetes and weight management that have been shown to result in substantial weight loss; however, studies of their effects in PWH are limited.Methods A retrospective single-center cohort study was conducted among PWH who were taking GLP-1RAs at UC San Diego Owen Clinic between 2/1/2021 to 2/1/2023. Baseline clinical data were collected and changes in weight, body mass index (BMI), and hemoglobin A1C (A1C) before starting GLP-1RAs compared to the most recent clinic visit were calculated (with a minimum of 3 months follow-up time required). Logistic regression was performed to identify variables associated with >5% of total body weight loss.Results A total of 225 patients received on average 13 months of GLP-1RA therapy, with 85 (37.8%) achieving the maximum GLP-1RA dose. GLP-1RA therapy resulted, on average, in a loss of 5.4 kg, decrease in BMI by 1.8 kg/m2, and decrease in A1C by 0.6%. In the multivariable analysis, higher baseline BMI [OR 1.10 (1.03-1.16)], treatment duration of GLP-1RA therapy greater than 6 months [OR 3.12 (1.49-6.49], and use of tirzepatide [OR 5.46 (1.44-20.76)] were significantly more likely to be associated with >5% weight loss.Conclusions Use of GLP-1RAs led to declines in weight, BMI, and hemoglobin A1C among PWH and offers an additional strategy to address weight gain and diabetes.
Læs mere Tjek på PubMedClinical Infectious Diseases, 19.03.2024
Tilføjet 19.03.2024
Somayaji, R., Luke, D. R., Lau, A., Guner, R., Tabak, O. F., Hepokoski, M., Gardetto, N., Conrad, S. A., Kumar, S. D., Ghosh, K., Robbins, S. M., Senger, D. L., Sun, D., Lim, R. K. S., Liu, J., Eser, F., Karaali, R., Tremblay, A., Muruve, D.
BMJ Open, 15.03.2024
Tilføjet 15.03.2024
ObjectiveDipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19. DesignPhase 2a randomised, placebo-controlled, double-blinded, trial. SettingHospitals in Canada, Turkey and the USA. ParticipantsA total of 61 subjects with moderate-to-severe COVID-19. InterventionsRandomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. Primary and secondary outcome measuresThe primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers. ResultsAt 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups. ConclusionIn a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. Trial registration numberNCT04402957.
Læs mere Tjek på PubMedSomayaji, R., Luke, D. R., Lau, A., Guner, R., Tabak, O. F., Hepokoski, M., Gardetto, N., Conrad, S. A., Kumar, S. D., Ghosh, K., Robbins, S. M., Senger, D. L., Sun, D., Lim, R. K. S., Liu, J., Eser, F., Karaali, R., Tremblay, A., Muruve, D.
BMJ Open, 15.03.2024
Tilføjet 15.03.2024
ObjectiveDipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19. DesignPhase 2a randomised, placebo-controlled, double-blinded, trial. SettingHospitals in Canada, Turkey and the USA. ParticipantsA total of 61 subjects with moderate-to-severe COVID-19. InterventionsRandomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. Primary and secondary outcome measuresThe primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers. ResultsAt 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups. ConclusionIn a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. Trial registration numberNCT04402957.
Læs mere Tjek på PubMedSomayaji, R., Luke, D. R., Lau, A., Guner, R., Tabak, O. F., Hepokoski, M., Gardetto, N., Conrad, S. A., Kumar, S. D., Ghosh, K., Robbins, S. M., Senger, D. L., Sun, D., Lim, R. K. S., Liu, J., Eser, F., Karaali, R., Tremblay, A., Muruve, D.
BMJ Open, 15.03.2024
Tilføjet 15.03.2024
ObjectiveDipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19. DesignPhase 2a randomised, placebo-controlled, double-blinded, trial. SettingHospitals in Canada, Turkey and the USA. ParticipantsA total of 61 subjects with moderate-to-severe COVID-19. InterventionsRandomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. Primary and secondary outcome measuresThe primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers. ResultsAt 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups. ConclusionIn a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. Trial registration numberNCT04402957.
Læs mere Tjek på PubMedClinical Infectious Diseases, 14.03.2024
Tilføjet 14.03.2024
Abstract Background A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman–Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab®) and the human diploid cell vaccine (HDCV; Imovax Rabies®).Methods This dual-center, modified double-blind, phase III study in France evaluated immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG), compared with PVRV+HRIG and HDCV+HRIG, in a simulated post-exposure prophylaxis (PEP) regimen. Healthy adults ≥18 years old (N=640) were randomized 3:1:1:1 to receive PVRV-NG2+HRIG, PVRV+HRIG, HDCV+HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, 3, 7, 14, and 28, with HRIG administered on D0 in applicable groups). Rabies virus neutralizing antibodies (RVNA titers) were assessed pre- (D0) and post-vaccination (D14, D28, and D42) using the rapid fluorescent focus inhibition test. Non-inferiority, based on the proportion of participants achieving RVNA titers ≥0.5 IU/mL (primary objective), was demonstrated if the lower limit of the 95% CI of the difference in proportions between PVRV-NG2+HRIG and PVRV+HRIG/HDCV+HRIG was >−5% at D28. Safety was assessed up to 6 months after the last injection.Results The non-inferiority of PVRV-NG2+HRIG, compared with PVRV+HRIG and HDCV+HRIG, was demonstrated. Nearly all participants (99.6%, PVRV-NG2+HRIG; 100%, PVRV+HRIG; 98.7%, HDCV+HRIG; 100%, PVRV-NG2 alone) achieved RVNA titers ≥0.5 IU/mL at D28. Geometric mean titers were similar between groups with concomitant HRIG administration at all time points. Safety profiles were similar between PVRV-NG2 and comparator vaccines.Conclusions In a simulated PEP setting, PVRV-NG2+HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines.Clinical Trials Registration NCT03965962.
Læs mere Tjek på PubMedMalaria Journal, 14.03.2024
Tilføjet 14.03.2024
Abstract Background The Great Mekong Subregion has attained a major decline in malaria cases and fatalities over the last years, but residual transmission hotspots remain, supposedly fueled by forest workers and migrant populations. This study aimed to: (i) characterize the fine-scale mobility of forest-goers and understand links between their daily movement patterns and malaria transmission, using parasites detection via real time polymerase chain reaction (RT PCR) and the individual exposure to Anopheles bites by quantification of anti-Anopheles saliva antibodies via enzyme-linked immunosorbent assay; (ii) assess the concordance of questionnaires and Global Positioning System (GPS) data loggers for measuring mobility. Methods Two 28 day follow-ups during dry and rainy seasons, including a GPS tracking, questionnaires and health examinations, were performed on male forest goers representing the population at highest risk of infection. Their time spent in different land use categories and demographic data were analyzed in order to understand the risk factors driving malaria in the study area. Results Malaria risk varied with village forest cover and at a resolution of only a few kilometers: participants from villages outside the forest had the highest malaria prevalence compared to participants from forest fringe’s villages. The time spent in a specific environment did not modulate the risk of malaria, in particular the time spent in forest was not associated with a higher probability to detect malaria among forest-goers. The levels of antibody response to Anopheles salivary peptide among participants were significantly higher during the rainy season, in accordance with Anopheles mosquito density variation, but was not affected by sociodemographic and mobility factors. The agreement between GPS and self-reported data was only 61.9% in reporting each kind of visited environment. Conclusions In a context of residual malaria transmission which was mainly depicted by P. vivax asymptomatic infections, the implementation of questionnaires, GPS data-loggers and quantification of anti-saliva Anopheles antibodies on the high-risk group were not powerful enough to detect malaria risk factors associated with different mobility behaviours or time spent in various environments. The joint implementation of GPS trackers and questionnaires allowed to highlight the limitations of both methodologies and the benefits of using them together. New detection and follow-up strategies are still called for.
Læs mere Tjek på PubMedJi Woong Kim, Ji Hyun Lee, Hyun Jung Kim, Kyun Heo, Yoonwoo Lee, Hui Jeong Jang, Ho‐Young Lee, Jun Won Park, Yea Bin Cho, Ha Gyeong Shin, Ha Rim Yang, Hee Eon Lee, Jin Young Song, Sukmook Lee
Journal of Medical Virology, 7.03.2024
Tilføjet 7.03.2024
Zhiyi LiaoChaoming WangXiaopeng TangMengli YangZilei DuanLei LiuShuaiyao LuLei MaRuomei ChengGan WangHongqi LiuShuo YangJingwen XuDawit Adisu TadeseJames MwangiPeter Muiruri KamauZhiye ZhangLian YangGuoyang LiaoXudong ZhaoXiaozhong PengRen LaiaEngineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), and Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650201, ChinabKunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, ChinacSchool of Basic Medicine, Qingdao University, Qingdao 266071, ChinadInstitute of Medical Biology, Chinese Academy of Medical Sciences, Kunming 650118, ChinaeLaboratory of Animal Tumor Models, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, ChinafKunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China
Proceedings of the National Academy of Sciences, 6.03.2024
Tilføjet 6.03.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 10, March 2024.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 5.03.2024
Tilføjet 5.03.2024
Abstract We previously described a novel Plasmodium vivax invasion mechanism into human reticulocytes via the PvRBP2a-CD98 receptor-ligand pair. We assessed the PvRBP2a epitopes involved in CD98 binding and recognised by antibodies from infected patients using linear epitope mapping. We identified two epitope clusters mediating PvRBP2a-CD98 interaction. One cluster named cluster B (PvRBP2a431-448, TAALKEKGKLLANLYNKL) was the target of antibody responses in P. vivax-infected humans. Peptides from each cluster were able to prevent live parasite invasion of human reticulocytes. These results provide new insights for development of a malaria blood stage vaccine against P. vivax.
Læs mere Tjek på PubMedWiseman, Robyn L.; Bigos, Kristin L.; Dastgheyb, Raha M.; Barker, Peter B.; Rubin, Leah H.; Slusher, Barbara S.
AIDS, 2.03.2024
Tilføjet 2.03.2024
Objectives : Cognitive impairment persists in virally-suppressed people with HIV (VS-PWH) especially in higher order domains. One cortical circuit, linked to these domains, is regulated by N-acetyl-aspartyl glutamate (NAAG), the endogenous agonist of the metabotropic glutamate receptor 3. The enzyme glutamate carboxypeptidase II (GCPII) catabolizes NAAG and is upregulated in aging and disease. Inhibition of GCPII increases brain NAAG and improves learning and memory in rodent and primate models. Design: As higher-order cognitive impairment is present in VS-PWH, and NAAG has not been investigated in earlier magnetic resonance spectroscopy studies (MRS), we investigated if brain NAAG levels measured by MRS were associated with cognitive function. Methods: We conducted a retrospective analysis of 7-Tesla MRS data from a previously published study on cognition in older VS-PWH. The original study did not separately quantify NAAG, therefore work for this report focused on relationships between regional NAAG levels in frontal white matter (FWM), left hippocampus, left basal ganglia and domain-specific cognitive performance in 40 VS-PWH after adjusting for confounds. Participants were >50 years of age, negative for affective and neurologic disorders, and had no prior 3-month psychoactive-substance use. Results: Higher NAAG levels in FWM were associated with better attention/working memory. Higher left basal ganglia NAAG related to better verbal fluency. There was a positive relationship between hippocampal NAAG and executive function which lost significance after correction for confounds. Conclusions: These data suggest brain NAAG serves as a biomarker of cognition in VS-PWH. Pharmacological modulation of brain NAAG warrants investigation as a therapeutic approach for cognitive deficits in VS-PWH. Conclusions: These data suggest brain NAAG serves as a biomarker of cognition in VS-PWH. Pharmacological modulation of brain NAAG warrants investigation as a therapeutic approach for cognitive deficits in VS-PWH. Graphical_abstract http://links.lww.com/QAD/D137 Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Læs mere Tjek på PubMedMiao ZhangBingqing YangJingru ShiZhiqiang WangYuan Liu1Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, China2Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, China3Institute of Comparative Medicine, Yangzhou University, Yangzhou, China, Anne-Catrin Uhlemann
Antimicrobial Agents And Chemotherapy, 29.02.2024
Tilføjet 29.02.2024
Charanpreet Kaur, Kandala Pavan Asrith, S. G. Ramachandra, Nagendra R. Hegde
PLoS One Infectious Diseases, 28.02.2024
Tilføjet 28.02.2024
by Charanpreet Kaur, Kandala Pavan Asrith, S. G. Ramachandra, Nagendra R. Hegde Subclinical infection of laboratory animals with one or more of several pathogens affects the results of experiments on animals. Monitoring the health of laboratory animals encompasses routine surveillance for pathogens, including several viruses. This study aimed to explore the development of an alternative assay to the existing ones for detecting infection of mice and rats with the parvoviruses minute virus of mice (MVM) and Kilham rat virus (KRV), respectively. Full-length VP2 and NS1 proteins of these parvoviruses, besides fragments containing multiple predicted epitopes stitched together, were studied for serological detection. The optimal dilution of full-length proteins and antigenic regions containing predicted epitopes for coating, test sera, and conjugate was determined using a checkerboard titration at each step. The assays were evaluated vis-à-vis commercially available ELISA kits. The results showed that an engineered fusion of fragments containing multiple predicted MVM VP2 and NS1 epitopes was better than either of the full-length proteins for detecting antibodies in 90% of the tested sera samples. For KRV ELISA, full-length VP2 was better compared to other individual recombinant protein fragments or combinations thereof for the detection of antibodies in sera. This report is the first description of an ELISA for KRV and an improved assay for MVM. Importantly, our assays could be exploited with small volumes of sera. The results also demonstrate the utility of immunoinformatics-driven polypeptide engineering in the development of diagnostic assays and the potential to develop better tests for monitoring the health status of laboratory animals.
Læs mere Tjek på PubMedAndrew MulatoEric LansdonRon AoyamaJohannes VoigtMichael LeeAlbert LiclicanGary LeeEric SingerBrian StaffordRuoyu GongBernard MurrayJulie ChanJohnny LeeYili XuShekeba AhmadyarAna GonzalezAesop ChoGeorge J. StepanUli SchmitzBrian SchultzBruno MarchandBoris BrumshteinRuth WangHelen YuTomas CihlarLianhong XuStephen R. Yant1Department of Virology, Gilead Sciences, Foster City, California, USA2Department of Structural Biology and Chemistry, Gilead Sciences, Foster City, California, USA3Department of Drug Metabolism, Gilead Sciences, Foster City, California, USA4Department of Discovery Sciences and Technology, Gilead Sciences, Foster City, California, USA5Department of Medicinal Chemistry, Gilead Sciences, Foster City, California, USA, Miguel Angel Martinez
Antimicrobial Agents And Chemotherapy, 22.02.2024
Tilføjet 22.02.2024
Chris Kenyon
International Journal of Infectious Diseases, 21.02.2024
Tilføjet 21.02.2024
Three randomized controlled trials have found that doxycycline post exposure prophylaxis (doxy-PEP) can reduce the incidence of gonorrhoea, chlamydia and syphilis in men who have sex with men (MSM) [1]. As a result, a number of international organizations suggest that doxy-PEP should be considered for use by MSM at risk [1].
Læs mere Tjek på PubMedBMC Infectious Diseases, 21.02.2024
Tilføjet 21.02.2024
Abstract Background Leprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP. Methods The PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 − 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 − 600 mg) and clarithromycin (150 − 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox’ proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome. Discussion Past studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities. Trial registration NL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060
Læs mere Tjek på PubMedJournal of Infectious Diseases, 20.02.2024
Tilføjet 20.02.2024
Abstract Background Lysins (cell wall hydrolases) targeting Gram-negative organisms require engineering to permeabilize the outer membrane and access subjacent peptidoglycan to facilitate killing. In the current study, the potential clinical utility for engineered lysin, CF-370, was examined in vitro and in vivo against Gram-negative pathogens important in human infections.Methods MICs and bactericidal activity were determined using standard methods. An in vivo proof-of-concept efficacy study was conducted using a rabbit acute pneumonia model caused by Pseudomonas aeruginosa.Results CF-370 exhibited potent antimicrobial activity, with MIC50/90 values (in µg/mL) for: P. aeruginosa, 1/2; Acinetobacter baumannii, 1/1; Escherichia coli, 0.25/1; Klebsiella pneumoniae, 2/4; Enterobacter cloacae 1/4; and Stenotrophomonas maltophilia 2/8. CF-370 furthermore demonstrated: i) bactericidal activity; (ii) activity in serum; iii) a low propensity for resistance; iv) anti-biofilm activity; and v) synergy with antibiotics. In the pneumonia model, CF-370 alone decreased bacterial densities in lungs, kidneys and spleen vs. vehicle control, and demonstrated significantly increased efficacy when combined with meropenem (vs either agent alone).Conclusions CF-370 is the first engineered lysin described with potent broad spectrum in vitro activity against multiple clinically-relevant Gram-negative pathogens, as well as potent in vivo efficacy in an animal model of severe invasive multi-system infection.
Læs mere Tjek på PubMedBolanaki, Myrto; Winning, Johannes; Slagman, Anna; Lehmann, Thomas; Kiehntopf, Michael; Stacke, Angelika; Neumann, Caroline; Reinhart, Konrad; Möckel, Martin; Bauer, Michael
Critical Care Medicine, 15.02.2024
Tilføjet 15.02.2024
Objectives: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. Design: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. Setting: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). Patients: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. Interventions: None. Measurements and Main Results: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79–0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. Conclusions: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.
Læs mere Tjek på PubMedBMC Infectious Diseases, 14.02.2024
Tilføjet 14.02.2024
Abstract Background Food borne diseases is a challenging problem nowadays. Salmonella and Shigella species are great concern of food-born outbreaks. Thus, this study was aimed to assess the prevalence, antimicrobial susceptibility test and associated factors of Salmonella and Shigella species in fruit juices and salads. Methods A community based cross sectional study design was carried out on 50 juice houses from December to March 2020 in Mekelle. One hundred fifty samples were collected aseptically from the juice houses for laboratory analysis. Information related to risk factors was obtained using a structured questionnaire. In the laboratory, samples were homogenized using peptone water and incubated overnight for enrichment. Then, Salmonella and Shigella species were isolated on Salmonella-Shigella agar and Xylose Lysine Deoxycholate agar. Disc diffusion method was used to perform antimicrobial susceptibility test. Using SPSS (version 22) package, descriptive statistics and Chi square test (χ2) were used to analyze the data, and p
Læs mere Tjek på PubMedGroele, L., Dzygało, K., Kowalska, A., Szypowska, A.
BMJ Open, 10.02.2024
Tilføjet 10.02.2024
IntroductionSphingolipids regulate proinsulin folding, insulin secretion and control beta cells apoptosis. Recent evidence has demonstrated that, among other factors, reduced amounts of sulfatide may be relevant in the development of type 1 diabetes (T1D). Thus, fenofibrate, which activates sulfatide biosynthesis, may prolong remission in subjects with T1D. The aim of the study is to evaluate clinical efficacy of fenofibrate on the maintenance of residual beta-cell function in children with newly diagnosed T1D. Methods and analysisA total of 102 children aged 10–17 years with newly diagnosed T1D will be enrolled in a double-blind, two-centre randomised, non-commercial, placebo-controlled trial. Subjects who will meet all inclusion criteria will be randomly assigned to receive fenofibrate at a dose of 160 mg or an identically appearing placebo, orally, once daily, for 12 months. The primary endpoint will be the area under the curve of the C-peptide level during 2-hour responses to a mixed-meal tolerance test (MMTT). Secondary endpoints include fasting and maximum C-peptide concentration in the MMTT, parameters of diabetes control and glucose fluctuations, daily insulin requirement, inflammation markers, genetic analysis, safety and tolerance of the fenofibrate Ethics and disseminationThe study protocol was approved by the Bioethics Committee. The results of this study will be submitted to a peer-reviewed diabetic journal. Abstracts will be submitted to international and national conferences. Trial registration numberEnduraCT 2020-003916-28.
Læs mere Tjek på PubMedClinical Infectious Diseases, 10.02.2024
Tilføjet 10.02.2024
Abstract Over the past two decades, cases of sexually transmitted infections (STIs) due to syphilis, gonorrhea, and chlamydia have been rising in the United States, disproportionately among gay, bisexual, and other men who have sex with men (MSM), as well as racial and ethnic minorities of all genders. In this review, we address updates about the evidence on doxycycline post-exposure prophylaxis (doxy-PEP) for prevention of bacterial STIs, including efficacy, safety, antimicrobial resistance (AMR), acceptability, modeling population impact, and evolving guidelines for use. Equitable implementation of doxy-PEP will require evaluation of who is offered and initiates it, understanding patterns of use and longer-term STI incidence and AMR, provider training, and tailored community education.
Læs mere Tjek på PubMedTomáš Scholz, Nadav Davidovich
Trends in Parasitology, 9.02.2024
Tilføjet 9.02.2024
The tapeworm Amirthalingamia macracantha is a parasite of African cormorants whose larvae infect tilapia and other cichlids. Tilapia are the second most important group of farmed fish worldwide. Over the course of a few years, this parasite has successfully spread to the Middle East, infecting fish and bird populations there. This is a unique example of accelerated spillover (‘pathogen pollution’) of an alien parasite with a complex life cycle involving three hosts (copepods – fish – birds). Considering the size of the larvae (up to 2 cm) and their localisation in the liver, this parasite poses a potential threat to local communities of wild, endangered cichlids and farmed tilapia.
Læs mere Tjek på PubMedJulián Fernando Oviedo-León, Maribel Cornejo-Mazón, Rosario Ortiz-Hernández, Nayeli Torres-Ramírez, Humberto Hernández-Sánchez, Diana C. Castro-Rodríguez
PLoS One Infectious Diseases, 7.02.2024
Tilføjet 7.02.2024
by Julián Fernando Oviedo-León, Maribel Cornejo-Mazón, Rosario Ortiz-Hernández, Nayeli Torres-Ramírez, Humberto Hernández-Sánchez, Diana C. Castro-Rodríguez Due to the distinctive characteristics of probiotics, it is essential to pinpoint strains originating from diverse sources that prove efficacious in addressing a range of pathologies linked to dysfunction of the intestinal barrier. Nine strains of lactic acid bacteria were isolated from two different sources of tepache kefir grains (KAS2, KAS3, KAS4, KAS7, KAL4, KBS2, KBS3, KBL1 and KBL3), and were categorized to the genus Lacticaseibacillus, Liquorilactobacillus, and Lentilactobacillus by 16S rRNA gene. Kinetic behaviors of these strains were evaluated in MRS medium, and their probiotic potential was performed: resistance to low pH, tolerance to pepsin, pancreatin, bile salts, antibiotic resistance, hemolytic activity, and adhesion ability. KAS7 strain presented a higher growth rate (0.50 h-1) compared with KAS2 strain, who presented a lower growth rate (0.29 h-1). KBS2 strain was the only strain that survived the in vitro stomach simulation conditions (29.3%). Strain KBL1 demonstrated significantly higher viability (90.6%) in the in vitro intestine simulation conditions. Strain KAS2 demonstrated strong hydrophilic character with chloroform (85.6%) and xylol (57.6%) and a higher percentage of mucin adhesion (87.1%). However, strains KBS2 (84.8%) and KBL3 (89.5%) showed the highest autoaggregation values. In terms of adhesion to the intestinal epithelium in rats, strains KAS2, KAS3 and KAS4 showed values above 80%. The growth of the strains KAS2, KAS3, KAS4, KBS2, and KBL3 was inhibited by cefuroxime, cefotaxime, tetracycline, ampicillin, erythromycin, and cephalothin. Strains KBS2 (41.9% and 33.5%) and KBL3 (42.5% and 32.8%) had the highest co-aggregation values with S. aureus and E. coli. The results obtained in this study indicate that lactic acid bacteria isolated from tepache can be considered as candidates for potentially probiotic bacteria, laying the foundations to evaluate their probiotic functionality in vivo and thus to be used in the formulation of functional foods.
Læs mere Tjek på PubMedJoshua Osowicki, Fergus Hamilton, Todd C. Lee, Michael Marks, Erin K. McCreary, Emily G. McDonald, Jonathan H. Ryder, Steven YC. Tong
Clinical Microbiology and Infection, 7.02.2024
Tilføjet 7.02.2024
The spectre of severe invasive infections caused by Streptococcus pyogenes and Staphylococcus aureus haunt clinicians and patients alike. They are the quintessential causes of devastating high profile ‘front page sepsis’ cases affecting children and adults, often without recognised risk factors, and typically associated with toxic shock syndromes (TSS) and necrotizing soft tissue infections (NSTI), as seen in the global surge of invasive S. pyogenes disease from late 2022.(1) These fulminant clinical syndromes demand rapid empiric antibiotic treatment and urgent surgical intervention for source control.
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