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BMC Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
Abstract Introduction Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhoea. Fidaxomicin and fecal microbiota transplantation (FMT) are effective, but expensive therapies to treat recurrent CDI (reCDI). Our objective was to develop a prediction model for reCDI based on the gut microbiota composition and clinical characteristics, to identify patients who could benefit from early treatment with fidaxomicin or FMT. Methods Multicentre, prospective, observational study in adult patients diagnosed with a primary episode of CDI. Fecal samples and clinical data were collected prior to, and after 5 days of CDI treatment. Follow-up duration was 8 weeks. Microbiota composition was analysed by IS-pro, a bacterial profiling technique based on phylum- and species-specific differences in the 16–23 S interspace regions of ribosomal DNA. Bayesian additive regression trees (BART) and adaptive group-regularized logistic ridge regression (AGRR) were used to construct prediction models for reCDI. Results 209 patients were included, of which 25% developed reCDI. Variables related to microbiota composition provided better prediction of reCDI and were preferentially selected over clinical factors in joint prediction models. Bacteroidetes abundance and diversity after start of CDI treatment, and the increase in Proteobacteria diversity relative to baseline, were the most robust predictors of reCDI. The sensitivity and specificity of a BART model including these factors were 95% and 78%, but these dropped to 67% and 62% in out-of-sample prediction. Conclusion Early microbiota response to CDI treatment is a better predictor of reCDI than clinical prognostic factors, but not yet sufficient enough to predict reCDI in daily practice.
Læs mere Tjek på PubMedBMC Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
Abstract Background Uganda has a sentinel surveillance system in seven high-risk sites to monitor yellow fever (YF) patterns and detect outbreaks. We evaluated the performance of this system from 2017 to 2022. Methods We evaluated selected attributes, including timeliness (lags between different critical time points), external completeness (proportion of expected sentinel sites reporting ≥ 1 suspect case in the system annually), and internal completeness (proportion of reports with the minimum required data elements filled), using secondary data in the YF surveillance database from January 2017–July 2022. We conducted key informant interviews with stakeholders at health facility and national level to assess usefulness, flexibility, simplicity, and acceptability of the surveillance system. Results In total, 3,073 suspected and 15 confirmed YF cases were reported. The median time lag from sample collection to laboratory shipment was 37 days (IQR:21–54). External completeness was 76%; internal completeness was 65%. Stakeholders felt that the surveillance system was simple and acceptable, but were uncertain about flexibility. Most (71%) YF cases in previous outbreaks were detected through the sentinel surveillance system; data were used to inform interventions such as intensified YF vaccination. Conclusion The YF sentinel surveillance system was useful in detecting outbreaks and informing public health action. Delays in case confirmation and incomplete data compromised its overall effectiveness and efficiency.
Læs mere Tjek på PubMedGuillaume Hoffmann, Maria Lukarska, Rachel H. Clare, Ellen K.G. Masters, Kelly L. Johnston, Louise Ford, Joseph D. Turner, Steve A. Ward, Mark J. Taylor, Malene Ringkjøbing Jensen, Andrés Palencia
Science Advances, 11.07.2024
Tilføjet 11.07.2024
Clinical Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
Clinical Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
Clinical Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) down-regulates angiotensin-converting enzyme 2, potentially increasing angiotensin II. We hypothesized that losartan compared to usual care decreases mortality and is safe in patients hospitalized with coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of losartan versus usual care on 28-day mortality in patients hospitalized for acute COVID-19.Methods Eligibility criteria included adults admitted for acute COVID-19. Exclusion criteria were hypotension, hyperkalemia, acute kidney injury, and use of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors within 7 days. Participants were randomized to losartan 25–100 mg/day orally for the hospital duration or 3 months or the control arm (usual care) in 29 hospitals in Canada and France. The primary outcome was 28-day mortality. Secondary outcomes were hospital mortality, organ support, and serious adverse events (SAEs).Results The trial was stopped early because of a serious safety concern with losartan. In 341 patients, any SAE and hypotension were significantly higher in the losartan versus usual care groups (any SAE: 39.8% vs 27.2%, respectively, P = .01; hypotension: 30.4% vs 15.3%, respectively, P < .001) in both ward and intensive care patients. The 28-day mortality did not differ between losartan (6.5%) versus usual care (5.9%) (odds ratio, 1.11 [95% confidence interval, .47–2.64]; P = .81), nor did organ dysfunction or secondary outcomes.Conclusions Caution is needed in deciding which patients to start or continue using ARBs in patients hospitalized with pneumonia to mitigate risk of hypotension, acute kidney injury, and other side effects. ARBs should not be added to care of patients hospitalized for acute COVID-19.Clinical Trials Registration NCT04606563.
Læs mere Tjek på PubMedChittappen K. Prajeeth Isabel Zdora Giulietta Saletti Julia Friese Thomas Gerlach Lucas Wilken Jana Beicht Mareike Kubinski Christina Puff Wolfgang Baumgärtner Jeroen Kortekaas Paul J. Wichgers Schreur Albert D.M.E. Osterhaus Guus F. Rimmelzwaan a Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germanyb Department of Pathology, University of Veterinary Medicine Hannover, Foundation, Hannover, Germanyc Leibniz Institute of Virology (LIV), Hamburg, Germanyd Department of Virology and Molecular Biology, Wageningen Bioveterinary Research, Wageningen University & Research, Lelystad, The Netherlandse Boehringer Ingelheim Animal Health, Global Innovation, Saint Priest, Francef BunyaVax B.V., Lelystad, The Netherlands
Emerg Microbes Infect, 11.07.2024
Tilføjet 11.07.2024
Zhiwei Zhao Tingting Yang Guoxiu Xiang Shebin Zhang Yimei Cai Guosheng Zhong Jieying Pu Cong Shen Jianming Zeng Cha Chen Bin Huang a Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of Chinab The Second Clinical Medical College, Guangzhou University of Chinese Medicine, State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of Chinac Department of Clinical Laboratory, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of Chinad Guangdong Provincial Key Laboratory of Research on Emergency in TCM, Guangzhou, People’s Republic of Chinae Department of Clinical Laboratory, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
Emerg Microbes Infect, 11.07.2024
Tilføjet 11.07.2024
International Journal for Parasitology, 11.07.2024
Tilføjet 11.07.2024
Publication date: Available online 9 July 2024 Source: International Journal for Parasitology Author(s): Pavel B. Klimov, Jan Hubert, Tomas Erban, M. Alejandra Perotti, Henk R. Braig, Alex Flynt, Qixin He, Yubao Cui
Læs mere Tjek på PubMedAndrew B. Lawson, Joanne Kim
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
Muhammad Rooman, Yasir Assad, Sadia Tabassum, Samia Sultan, Sultan Ayaz, Muhammad Fiaz Khan, Shahid Niaz Khan, Rehman Ali
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
by Muhammad Rooman, Yasir Assad, Sadia Tabassum, Samia Sultan, Sultan Ayaz, Muhammad Fiaz Khan, Shahid Niaz Khan, Rehman Ali
Læs mere Tjek på PubMedLeyre Sánchez-Barrionuevo, Alejandro González-Benjumea, Almudena Escobar-Niño, María Teresa García, Óscar López, Inés Maya, José G. Fernández-Bolaños, David Cánovas, Encarnación Mellado
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
by Leyre Sánchez-Barrionuevo, Alejandro González-Benjumea, Almudena Escobar-Niño, María Teresa García, Óscar López, Inés Maya, José G. Fernández-Bolaños, David Cánovas, Encarnación Mellado
Læs mere Tjek på PubMedMaureen Sakoi-Mosetlhi, Gbolahan Ajibola, Roxanna Haghighat, Oganne Batlang, Kenneth Maswabi, Molly Pretorius-Holme, Kathleen M. Powis, Shahin Lockman, Joseph Makhema, Mathias Litcherfeld, Daniel R. Kuritzkes, Roger Shapiro
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
by Maureen Sakoi-Mosetlhi, Gbolahan Ajibola, Roxanna Haghighat, Oganne Batlang, Kenneth Maswabi, Molly Pretorius-Holme, Kathleen M. Powis, Shahin Lockman, Joseph Makhema, Mathias Litcherfeld, Daniel R. Kuritzkes, Roger Shapiro
Læs mere Tjek på PubMedFumio Takizawa, Hisanori Domon, Satoru Hirayama, Toshihito Isono, Karin Sasagawa, Daisuke Yonezawa, Akiomi Ushida, Satomi Tsutsuura, Tomohiro Miyoshi, Hitomi Mimuro, Akihiro Yoshida, Koichi Tabeta, Yutaka Terao
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
by Fumio Takizawa, Hisanori Domon, Satoru Hirayama, Toshihito Isono, Karin Sasagawa, Daisuke Yonezawa, Akiomi Ushida, Satomi Tsutsuura, Tomohiro Miyoshi, Hitomi Mimuro, Akihiro Yoshida, Koichi Tabeta, Yutaka Terao Infectious and foodborne diseases pose significant global threats, with devastating consequences in low- and middle-income countries. Ozone, derived from atmospheric oxygen, exerts antimicrobial effects against various microorganisms, and degrades fungal toxins, which were initially recognized in the healthcare and food industries. However, highly concentrated ozone gas can be detrimental to human health. In addition, ozonated water is unstable and has a short half-life. Therefore, ultrafine-bubble technology is expected to overcome these issues. Ultrafine bubbles, which are nanoscale entitles that exist in water for considerable durations, have previously demonstrated bactericidal effects against various bacterial species, including antibiotic-resistant strains. This present study investigated the effects of ozone ultrafine bubble water (OUFBW) on various bacterial toxins. This study revealed that OUFBW treatment abolished the toxicity of pneumolysin, a pneumococcal pore-forming toxin, and leukotoxin, a toxin that causes leukocyte injury. Silver staining confirmed the degradation of pneumolysin, leukotoxin, and staphylococcal enterotoxin A, which are potent gastrointestinal toxins, following OUFB treatment. In addition, OUFBW treatment significantly inhibited NF-κB activation by Pam3CSK4, a synthetic triacylated lipopeptide that activates Toll-like receptor 2. Additionally, OUFBW exerted bactericidal activity against Staphylococcus aureus, including an antibiotic-resistant strain, without displaying significant toxicity toward human neutrophils or erythrocytes. These results suggest that OUFBW not only sterilizes bacteria but also degrades bacterial toxins.
Læs mere Tjek på PubMedNok Chhun, Claire W. Rothschild, Monalisa Penumetsa, Daniel Matemo, Peninah Kithao, Barbra A. Richardson, Grace John-Stewart, John Kinuthia, Alison L. Drake
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
by Nok Chhun, Claire W. Rothschild, Monalisa Penumetsa, Daniel Matemo, Peninah Kithao, Barbra A. Richardson, Grace John-Stewart, John Kinuthia, Alison L. Drake Background Clinical risk score tools require validation in diverse settings and populations before they are widely implemented. We aimed to externally validate an HIV risk assessment tool for predicting HIV acquisition among pregnant and postpartum women. In the context of prevention of mother-to-child transmission programs, risk score tools could be used to prioritize retesting efforts and delivery of pre-exposure prophylaxis (PrEP) to pregnant and postpartum women most at risk for HIV acquisition while minimizing unnecessary perinatal exposure. Methods Data from women enrolled in a cross-sectional study of programmatic HIV retesting and/or receiving maternal and child health care services at five facilities in Western Kenya were used to validate the predictive ability of a simplified risk score previously developed for pregnant/postpartum women. Incident HIV infections were defined as new HIV diagnoses following confirmed negative or unknown status during pregnancy. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUC) and Brier score. Results Among 1266 women with 35 incident HIV infections, we found an AUC for predicting HIV acquisition of 0.60 (95% CI, 0.51, 0.69), with a Brier score of 0.27. A risk score >6 was associated with a 2.9-fold increase in the odds of HIV acquisition (95% CI, 1.48, 5.70; p = 0.002) vs scores ≤6. Women with risk scores >6 were 27% (346/1266) of the population but accounted for 52% of HIV acquisitions. Syphilis, age at sexual debut, and unknown partner HIV status were significantly associated with increased risk of HIV in this cohort. Conclusion The simplified risk score performed moderately at predicting risk of HIV acquisition in this population of pregnant and postpartum women and may be useful to guide PrEP use or counseling.
Læs mere Tjek på PubMedGemeda Wakgari Kitil, Abiy Tasew Dubale, Adamu Ambachew Shibabaw, Alex Ayenew Chereka
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
by Gemeda Wakgari Kitil, Abiy Tasew Dubale, Adamu Ambachew Shibabaw, Alex Ayenew Chereka Background Hepatitis B virus infection remains a significant public health concern globally, particularly among healthcare workers, including health science students who are at high risk due to their exposure to infected patients and contaminated medical equipment. In Ethiopia, where the burden of HBV infection is substantial, preventive practices among health science students are critical for minimizing transmission and ensuring a healthy workforce. However, there is a lack of comprehensive evidence regarding the effectiveness of these practices specifically among this population in Ethiopia. Therefore, this study aimed to provide a systematic review and meta-analysis of preventive measures for Hepatitis B infection among Health Science Students in Ethiopia. Methods This study followed the guidelines outlined in the PRISMA checklist and focused on research conducted within Ethiopia. Seven relevant studies were identified through comprehensive searches across various databases including Google, Medline, PubMed, and Scholar. Data retrieval was systematically conducted using a checklist, and analysis was performed using STATA version 14. Heterogeneity was assessed using both the Cochrane Q test and the I2 statistic. Additionally, publication bias was evaluated using Egger’s weighted regression, a funnel plot, and Begg’s test. Results In this meta-analysis and systematic review, we identified a total of 515 research articles, of which seven studies met the eligibility criteria for analysis. The overall pooled magnitude of practices aimed at preventing Hepatitis B infection among Health Science Students in Ethiopia was 41.21% (95% CI: 30.81–51.62). Factors significantly associated with these practices included better understanding of Hepatitis B infection prevention (OR = 1.99, 95% CI: 1.20–3.29), age group 20–24 years (OR = 5.79, 95% CI: 2.43–13.78), needle stick injury exposure (OR = 3.43, 95% CI: 1.10–10.70), and students enrolled in medicine or public health officer departments (OR = 4.20, 95% CI: 2.65–6.65). Conclusion Our analysis indicates that only 41.21% of Health Science students in Ethiopia adhere to Hepatitis B prevention practices. To improve these practices, it is essential to mandate vaccination, provide targeted training on infection prevention, and increase awareness of vaccine uptake. Tailored educational programs should equip students with practical strategies. Additionally, intelligent interventions must address factors influencing preventive practices. Collaboration between institutions and ongoing monitoring is crucial to ensuring success.
Læs mere Tjek på PubMedLiv Rabøl Andersen, Bettina Hindsberger, Simone Bastrup Israelsen, Lise Pedersen, Pal Bela Szecsi, Thomas Benfield
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
by Liv Rabøl Andersen, Bettina Hindsberger, Simone Bastrup Israelsen, Lise Pedersen, Pal Bela Szecsi, Thomas Benfield Introduction Immune dysregulation with an excessive release of cytokines has been identified as a key driver in the development of severe COVID-19. The aim of this study was to evaluate the initial cytokine profile associated with 90-day mortality and respiratory failure in a cohort of patients hospitalized with COVID 19 that did not receive immunomodulatory therapy. Methods Levels of 45 cytokines were measured in blood samples obtained at admission from patients with confirmed COVID-19. Logistic regression analysis was utilized to determine the association between cytokine levels and outcomes. The primary outcome was death within 90 days from admission and the secondary outcome was need for mechanical ventilation. Results A total of 132 patients were included during the spring of 2020. We found that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with the odds of 90-day mortality, specifically: interleukin-1 receptor antagonist, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-3α, macrophage inflammatory protein-3β, and fractalkine. All but fractalkine were also associated with the odds of respiratory failure during admission. Monocyte chemoattractant protein-1 showed the strongest estimate of association with both outcomes. Conclusion We showed that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with 90-day mortality in patients hospitalized with COVID-19 that did not receive immunomodulatory therapy.
Læs mere Tjek på PubMedJianlong Xie, Zhirong Ye, Xiaobing Xu, Anzhi Chang, Ziyi Yang, Qin Wu, Qunwen Pan, Yan Wang, Yanyu Chen, Xiaotang Ma, Huilai Miao
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
by Jianlong Xie, Zhirong Ye, Xiaobing Xu, Anzhi Chang, Ziyi Yang, Qin Wu, Qunwen Pan, Yan Wang, Yanyu Chen, Xiaotang Ma, Huilai Miao Background This study evaluated the effect of microvesicles(MVs) from quiescent and TGF-β1 stimulated hepatic stellate cells (HSC-MVs, TGF-β1HSC-MVs) on H2O2-induced human umbilical vein endothelial cells (HUVECs) injury and CCl4-induced rat hepatic vascular injury. Methods HUVECs were exposed to hydrogen peroxide (H2O2) to establish a model for vascular endothelial cell injury. HSC-MVs or TGF-β1HSC-MVs were co-cultured with H2O2-treated HUVECs, respectively. Indicators including cell survival rate, apoptosis rate, oxidative stress, migration, invasion, and angiogenesis were measured. Simultaneously, the expression of proteins such as PI3K, AKT, MEK1+MEK2, ERK1+ERK2, VEGF, eNOS, and CXCR4 was assessed, along with activated caspase-3. SD rats were intraperitoneally injected with CCl4 twice a week for 10 weeks to induce liver injury models. HSC-MVs or TGF-β1HSC-MVs were injected into the tail vein of rats. Liver and hepatic vascular damage were also detected. Results In H2O2-treated HUVECs, HSC-MVs increased cell viability, reduced cytotoxicity and apoptosis, improved oxidative stress, migration, and angiogenesis, and upregulated protein expression of PI3K, AKT, MEK1/2, ERK1/2, VEGF, eNOS, and CXCR4. Conversely, TGF-β1HSC-MVs exhibited opposite effects. CCl4- induced rat hepatic injury model, HSC-MVs reduced the release of ALT and AST, hepatic inflammation, fatty deformation, and liver fibrosis. HSC-MVs also downregulated the protein expression of CD31 and CD34. Conversely, TGF-β1HSC-MVs demonstrated opposite effects. Conclusion HSC-MVs demonstrated a protective effect on H2O2-treated HUVECs and CCl4-induced rat hepatic injury, while TGF-β1HSC-MVs had an aggravating effect. The effects of MVs involve PI3K/AKT/VEGF, CXCR4, and MEK/ERK/eNOS pathways.
Læs mere Tjek på PubMedMatt A. Price, Monica Kuteesa, Matthew Oladimeji, William Brumskine, Vinodh Edward, Heeran Makkan, Funeka Mthembu, Vincent Muturi-Kioi, Candice Chetty-Makkan, Pholo Maenetje
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
by Matt A. Price, Monica Kuteesa, Matthew Oladimeji, William Brumskine, Vinodh Edward, Heeran Makkan, Funeka Mthembu, Vincent Muturi-Kioi, Candice Chetty-Makkan, Pholo Maenetje Adolescents face a higher risk for HIV, STIs, and unintended pregnancy than any other age group in sub–Saharan Africa, and have unique health care needs as they navigate this period of growth and developmental milestones. We conducted the Youth Friendly Services study among adolescents in Rustenburg, South Africa to address some of these concerns. Participants aged 12–19 were followed quarterly for 12 months, asked at baseline about demographics, their sexual behavior, and tested for HIV, STIs, and pregnancy (girls). Report of sexual activity was not a requirement for enrollment. Assent and parental consent were obtained for participants under 18. Some follow up visits fell during COVID-mandated shutdowns, and we worked with participants to reschedule and extend follow up as appropriate. Here we present data on reported behaviors, participant attrition, risk of HIV, other STI, and pregnancy. From May 2018 to August 2019, we enrolled 223 HIV-negative, non-pregnant adolescents (64% girls). The median age was 17 (IQR: 14–18). Among the 119 (53%) participants who reported being sexually active at baseline, the median age at first sex was 16 years (IQR: 15–17). During follow-up, an additional 16 (7%) participants reported having their first sexual encounter. Among the sexually active participants, the incidence of HIV was 1.5 cases / 100 person-years at risk (PYAR, 95% CI: 0.4–6.0), the incidence of chlamydia was 15.7 cases (95% CI: 10.1–24.4), gonorrhea was 4.7 cases (95% CI: 2.1–10.5), and HSV was 6.3 cases (95% CI: 3.1–12.6); we observed no cases of incident syphilis. The incidence of pregnancy among sexually active girls was 15.0 pregnancies / 100 PYAR (95% CI: 8.5–26.5). Despite small numbers, the incidence of most STIs was significantly higher in females compared to males. We also observed two pregnancies and 5 incident STIs among participants who reported never having had sex, these tended to be younger participants. From March to September 2020, the clinic was shut down for COVID-19, and 53 study visits were postponed. Follow up was concluded in November 2020, a total of 19 participants were lost to follow up, however only one participant dropped off-study during COVID-19 shutdowns. Retention at the final visit was 91.5%. We successfully completed a prospective study of adolescents to learn more about the risks they face as they navigate sexual debut in the context of a program of youth-friendly counseling and services. Among self-reported sexually active participants, we observed a high rate of HIV, STI and pregnancy, however we also observed pregnancy and STIs among those who reported no sexual activity.
Læs mere Tjek på PubMedAlemante Tafese Beyna, Assefa Kebad Mengesha, Ermias Teklehaimanot Yefter, Wubayehu Kahaliw
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
by Alemante Tafese Beyna, Assefa Kebad Mengesha, Ermias Teklehaimanot Yefter, Wubayehu Kahaliw Background Wounds significantly affect people’s quality of life and the clinical and financial burden of healthcare systems around the world. Many of the current drugs used to treat wounds have problems such as; allergies and drug resistance. Hence, the exploration of new therapeutic agents from natural origin may avert this problem. Clerodendrum myricoides have long been used to treat wounds in Ethiopia. Despite this, nothing has so far been reported about the wound healing and anti-inflammatory activity of C. myricoides. This study aimed to evaluate the wound healing and anti-inflammatory activity of 80% methanol extract and solvent fractions of C. myricoides leaves in mice. Methods Leaves of C. myricoides were extracted using the maceration technique. The extract was formulated as 5% and 10% w/w ointments. The wound healing activity of the extract was evaluated using excision, incision, and burn wound models whereas the healing activities of solvent fractions were evaluated using the excision wound model. A carrageenan-induced paw edema model was used for the anti-inflammatory test. Results In the dermal toxicity test, 2000 mg/kg of 10% extract was found to be safe. In excision and burn wound models, treatment with 10% and 5% extract showed a significant (p
Læs mere Tjek på PubMedCourtney E. Buchanan, Stephanie J. Galla, Mario E. Muscarella, Jennifer S. Forbey, Adele K. Reinking, Jeffrey L. Beck
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
by Courtney E. Buchanan, Stephanie J. Galla, Mario E. Muscarella, Jennifer S. Forbey, Adele K. Reinking, Jeffrey L. Beck Host microbial communities (hereafter, the ‘microbiome’) are recognized as an important aspect of host health and are gaining attention as a useful biomarker to understand the ecology and demographics of wildlife populations. Several studies indicate that the microbiome may contribute to the adaptive capacity of animals to changing environments associated with increasing habitat fragmentation and rapid climate change. To this end, we investigated the gut microbiome of pronghorn (Antilocapra americana), an iconic species in an environment that is undergoing both climatic and anthropogenic change. The bacterial composition of the pronghorn gut microbiome has yet to be described in the literature, and thus our study provides important baseline information about this species. We used 16S rRNA amplicon sequencing of fecal samples to characterize the gut microbiome of pronghorn—a facultative sagebrush (Artemisia spp.) specialist in many regions where they occur in western North America. We collected fecal pellets from 159 captured female pronghorn from four herds in the Red Desert of Wyoming during winters of 2013 and 2014. We found small, but significant differences in diversity of the gut microbiome relative to study area, capture period, and body fat measurements. In addition, we found a difference in gut microbiome composition in pronghorn across two regions separated by Interstate 80. Results indicated that the fecal microbiome may be a potential biomarker for the spatial ecology of free-ranging ungulates. The core gut microbiome of these animals—including bacteria in the phyla Firmicutes (now Bacillota) and Bacteroidota—remained relatively stable across populations and biological metrics. These findings provide a baseline for the gut microbiome of pronghorn that could potentially be used as a target in monitoring health and population structure of pronghorn relative to habitat fragmentation, climate change, and management practices.
Læs mere Tjek på PubMedDiana Celi, Evelyn Quiroz, Andrea Beltrán-Noboa, António Machado, Eduardo Tejera, Paulina Fernandez-Soto
PLoS One Infectious Diseases, 11.07.2024
Tilføjet 11.07.2024
by Diana Celi, Evelyn Quiroz, Andrea Beltrán-Noboa, António Machado, Eduardo Tejera, Paulina Fernandez-Soto The Pelargonium genus encompasses around 280 species, most of which are used for medicinal purposes. While P. graveolens, P. odoratissimum, and P. zonale are known to exhibit antimicrobial activity, there is an evident absence of studies evaluating all three species to understand their chemical differences and biological effects. Through the analysis of the hydroalcoholic extracts of P. graveolens, P. odoratissimum, and P. zonale, using HPLC-DAD-MS/MS, quercetin and kaempferol derivatives were identified in these three species. Conversely, gallotannins and anthocyanins were uniquely detected in P. zonale. P. graveolens stood out due to the various types of myricetin derivatives that were not detected in P. odoratissimum and P. zonale extracts. Evaluation of their biological activities revealed that P. zonale displayed superior antibacterial and antibiofilm activities in comparison to the other two species. The antibacterial efficacy of P. zonale was observed towards the clinically relevant strains of Staphylococcus aureus ATCC 25923, Methicillin-resistant Staphylococcus aureus (MRSA) 333, Enterococcus faecalis ATCC 29212, and the Vancomycin-resistant E. faecalis INSPI 032. Fractionation analysis of P. zonale suggested that the antibacterial activity attributed to this plant is due to the presence of quercetin derivatives and kaempferol and its derivatives, alongside their synergistic interaction with gallotannins and anthocyanins. Lastly, the three Pelargonium species exhibited notable antioxidant activity, which may be attributed to their high content of total phenolic compounds.
Læs mere Tjek på PubMedImmunity, 11.07.2024
Tilføjet 11.07.2024
Publication date: 9 July 2024 Source: Immunity, Volume 57, Issue 7 Author(s): Laurent Abel, Jean-Laurent Casanova
Læs mere Tjek på PubMedInfection, 10.07.2024
Tilføjet 10.07.2024
Abstract Epidemiology of shigellosis has drastically changed in recent years due to globalization and sexual risk behaviors. Here, through whole-genome sequencing, we characterized two ESBL-producing Shigella sonnei strains (ShSoBUH1 and ShSoBUH2) carrying a blaCTX−M−15 among men who have sex with men (MSM), who had not recently traveled and presented sexual risk behaviors. Both strains harbored IncB/O/K/Z and IncFII plasmids, which carry aadA1, aadA5, sul1, sul2, dfrA1, dfrA17, mph(A), erm(B), tet(B), qacE and blaCTX−M−15 genes conferring resistance to 2nd and 3rd generation cephalosporins, cotrimoxazole, erythromycin, azithromycin and quinolones. IncFII plasmids containing blaCTX−M−15 from ShSoBUH1 and ShSoBUH2 presented 99,8–99,9% similarity with plasmids from another five CTX-M-15 S. sonnei strains detected in Belgium and Switzerland. A single-nucleotide polymorphism (SNP) analysis determined that the study strains differed by 361 SNPs, belonging to different clusters. To the best of our knowledge, this is the first report describing two extensively drug-resistant (XDR) CTX-M-15 S. sonnei strains in MSM.
Læs mere Tjek på PubMedInfection, 10.07.2024
Tilføjet 10.07.2024
Abstract Purpose Diagnosis of (European) Lyme neuroborreliosis has been based on clinical presentation, cerebrospinal fluid (CSF) pleocytosis and demonstration of intrathecal borrelial antibody synthesis (ITBAS) to document Borrelia burgdorferi s. l. infection. It is not known if other criteria to document Borrelia infection may contribute to the diagnosis. Methods We compared the sensitivity of three individual criteria (ITBAS, CSF Borrelia culture, and the presence of erythema migrans [EM]) to confirm the diagnosis of early Lyme neuroborreliosis in 280 patients ≥ 15 years of age evaluated at a Lyme borreliosis outpatient clinic in Slovenia. The patients had either radicular pain of new onset or involvement of a cranial nerve but without radicular pain, each in conjunction with CSF pleocytosis. Evaluation was of patients who had each of the three confirmatory criteria assessed, and for whom at least one criterion was positive. Results Analysis of 280 patients, 120 women and 160 men, median age 57 (range 15–84) years, revealed that ITBAS was the most frequently observed positive criterion (85.4%), followed by EM (52.9%), and by a positive CSF Borrelia culture (9.6%). Of the 280 patients, 154 (55%) met only one criterion (43.2% ITBAS only, 10.7% EM only, and 1.1% positive CSF culture only), whereas 42.1% met two criteria. Only 2.9% of patients were positive by all three criteria. Conclusion Although ITBAS was the most frequent criterion for confirmation for Borrelia infection, the presence of EM alone confirmed an additional 10.7% of patients and a positive CSF Borrelia culture alone added another 1.1%.
Læs mere Tjek på PubMedInfection, 10.07.2024
Tilføjet 10.07.2024
Abstract Purpose Intestinal protozoan parasites among Asian schoolchildren are a subject of concern due to their prevalence and potential health impact. Understanding and addressing this issue is crucial for public health in the region. Methods We conducted a comprehensive search for articles published up to December 2023 across four databases, including Scopus, PubMed, ProQuest, and Web of Science. To estimate the combined prevalence, a random-effects model with a 95% confidence interval (CI) was applied, and the statistical analysis was performed using meta-analysis packages in R version (3.6.1). This study is registered with PROSPERO (CRD42023481146). Results Among 131 eligible articles, the prevalence of intestinal protozoan parasites was 0.208 (95% CI = 0.180–0.238). Lebanon and Tajikistan had the highest country-level prevalence at 0.851 and 0.836, respectively, with Giardia duodenalis being the most prevalent species at 0.082. Conclusion In summary, our study highlights the urgent public health issue of protozoan parasites among Asian schoolchildren due to poor sanitation and water quality. Immediate interventions are essential, considering climate and socioeconomic factors, to combat these infections and improve overall health.
Læs mere Tjek på PubMedInfection, 10.07.2024
Tilføjet 10.07.2024
Abstract Purpose Many curricula promote frontal teaching approaches, potentially decreasing interaction and motivation – also within infection prevention & control and infectious diseases (IPC/ID). We aimed to investigate the implementation of three innovative teaching methods (ITM) within IPC/ID education: game-based learning (GBL), peer-teaching (PT) and misinformation detection (MID). Methods Multi-phase study involving third-year medical students was conducted. Phase-1 included a cross-sectional survey, assessing previous ITM-experience and interest to participate in phase-2, where the students were divided into teams. Each team prepared a video covering an IPC/ID-topic with deliberately placed misinformation, which had to be identified and corrected by the opposing team, followed by qualitative evaluation (phase-3). Finally, the MID-concept was incorporated into regular curricula in a non-competitive environment (phase-4) and evaluated within a cohort not involved in phases 1–3. Results 276 students responded to phase-1. 58% expressed interest in participating in phase-2. Roughly 59% [47–71%] CI-95% of respondents without previous PT-experience stated interest in PT, while the interest in GBL and MID was even higher. 19 students participated in phase-2. All topic MID-scores ranged between 6 and 8/10 points, except for emporiatrics (3/10). Post-hoc analysis revealed a positive student-perception of ITM, particularly GBL. Phase-4 received 103 responses with general positive evaluation. Major agreements existed on the usefulness of critical information evaluation for medical practice (82% [75–91%] CI-95%) and of MID during studies (69% [59–79%] CI-95%). Conclusion our results hint at a relatively high interest in ITM and show MID applicability in regular IPC/ID curricula, which could be of advantage for the learning environment.
Læs mere Tjek på PubMedInfection, 10.07.2024
Tilføjet 10.07.2024
Infection, 10.07.2024
Tilføjet 10.07.2024
Infection, 10.07.2024
Tilføjet 10.07.2024
Abstract Purpose We aimed to develop and implement dosing recommendations for antimicrobials in obese and underweight patients within an academic hospital, and assess their impact on antibiotic prescribing. Methods A multi-step approach project was performed. First, obese and underweight patient prevalence and antimicrobial prescription frequency was determined in a point prevalence study. Second and third, a literature review and e-survey provided dosing evidence. Fourth, a consensus meeting was organized to formulate dosing recommendations. Fifth, these were implemented in our clinical validation service as six clinical rules continuously screening patients’ records for potentially inappropriate prescriptions (PIPs). Uptake was evaluated by documenting the number of advices and acceptance rate. Last, an interrupted time series analysis (ITS) compared pre- and post-implementation periods to measure the impact of the intervention on residual PIPs/day. A residual PIP was defined as a PIP which persisted up to 48 h. Results First, 41% of 15.896 hospitalized patients received antimicrobials over 20 days; of which 12% were obese and 9% underweight. Antibiotics were predominantly prescribed according to standard dosing regimens, adjusted to renal function. Next, six dosing recommendations, derived from literature, survey, and consensus, were implemented. In the fifth step, during an 18-week period, 219 advices were given, with 86% acceptance rate. Last, in the ITS analysis, at preintervention, a median of 75% residual PIPs/day existed, reduced to 0% postintervention. Use of clinical rules resulted in a significant immediate 84% relative reduction in residual PIPs (95% CI 0.55–0.94). Conclusion After conducting a literature review, e-survey, and seeking consensus from a panel of experts, dosing recommendations for antimicrobial treatment in both obese and underweight patients were developed. These recommendations have been successfully implemented into clinical practice, addressing the specific needs of these patient populations.
Læs mere Tjek på PubMedInfection, 10.07.2024
Tilføjet 10.07.2024
Infection, 10.07.2024
Tilføjet 10.07.2024
Abstract Purpose To characterize the clinical relevance of S. saccharolyticus and to identify criteria to distinguish between infection and contamination. Methods We retrospectively investigated clinical features of patients with S. saccharolyticus detection between June 2009 and July 2021. Based on six criteria, infection was considered likely for patients with a score from 3 to 6 points, infection was considered unlikely for patients with a score from 0 to 2 points. We performed group comparison and logistic regression to identify factors than are associated with likely infection. In addition, whole genome sequencing (WGS) of 22 isolates was performed. Results Of 93 patients in total, 44 were assigned to the group “infection likely” and 49 to the group “infection unlikely”. Multiple regression analysis revealed “maximum body temperature during hospital stay” to have the strongest predictive effect on likely infection (adjusted odds ratio 4.40, 95% confidence interval 2.07–9.23). WGS revealed two different clades. Compared to isolates from clade A, isolates from clade B were more frequently associated with implanted medical devices (3/10 vs. 9/12, p = 0.046) and a shorter time to positivity (TTP) (4.5 vs. 3, p = 0.016). Both clades did neither differ significantly in terms of causing a likely infection (clade A 7/10 vs. clade B 5/12, p = 0.23) nor in median length of hospital stay (28 vs. 15.5 days, p = 0.083) and length of stay at the ICU (21 vs. 3.5 days, p = 0.14). Conclusion These findings indicate that S. saccharolyticus can cause clinically relevant infections. Differentiation between infection and contamination remains challenging.
Læs mere Tjek på PubMedInfection, 10.07.2024
Tilføjet 10.07.2024
Abstract Purpose Listeria monocytogenes causes severe bacterial infections with the highest mortality rate among foodborne pathogens in Europe. Combination treatment with ampicillin and gentamicin is recommended for invasive manifestations. However, evidence to support this treatment approach remains limited due to a lack of randomised controlled trials. To explore this critical issue further, we conducted this retrospective, single-center study. Methods We identified all patients hospitalized with invasive listeriosis at the University Medical Center Hamburg-Eppendorf between 2009 and 2020 and analyzed the effect of gentamicin combination treatment versus monotherapy on 90-day mortality. Results In total, 36 patients with invasive listeriosis were included, of which 21 patients received gentamicin combination treatment and 15 received monotherapy. The mean age-adjusted Charlson Comorbidity Index (aaCCI) value was lower in the gentamicin combination treatment group (5.4 vs. 7.4). Neurolisteriosis was more common in the gentamicin group (81% vs. 20%). The 90-day mortality was with significantly lower in the gentamicin combination treatment group (10%) compared to the monotherapy group (60%). Multivariable cox regression analysis, adjusted for a propensity score computed based on neurolisteriosis, aaCCI and sex, revealed a significantly reduced hazard ratio of 0.07 (95% CI: 0.01–0.53, p = 0.01) for 90-day mortality for the gentamicin combination treatment. Conclusion This retrospective study highlights the benefit of gentamicin combination treatment in reducing the 90-day mortality rate among patients with invasive listeriosis. The high prevalence of monotherapy in this study cohort raises concerns about the adequacy of antibiotic therapy in clinical practice.
Læs mere Tjek på PubMedInfection, 10.07.2024
Tilføjet 10.07.2024
Abstract Paradoxical reactions (PR) to tuberculosis (TB) treatment are common during treatment, but have also been described after treatment. A presentation with recurrent signs or symptoms of TB after cure or completion of prior treatment needs to be differentiated between microbiological relapse and a paradoxical reaction. We searched all published literature on post-treatment PR, and present a synthesis of 30 studies, focusing on the epidemiology, diagnosis and management of this phenomenon. We report an additional case vignette. The majority of studies were of lymph node TB (LN-TB), followed by central nervous system TB (CNS-TB). A total of 112 confirmed and 42 possible post-treatment PR cases were reported. The incidence ranged between 3 and 14% in LN-TB and was more frequent than relapses, and between 0 and 2% in all TB. We found four reports of pulmonary or pleural TB post-treatment PR cases. The incidence did not differ by length of treatment, but was associated with younger age at initial diagnosis, and having had a PR (later) during treatment. Post-treatment PR developed mainly within the first 6 months after the end of TB treatment but has been reported many years later (longest report 10 years). The mainstays of diagnosis and management are negative mycobacterial cultures and anti-inflammatory treatment, respectively. Due to the favourable prognosis in LN-TB recurrent symptoms, a short period of observation is warranted to assess for spontaneous regression. In CNS-TB with recurrent symptoms, immediate investigation and anti-inflammatory treatment with the possibility of TB retreatment should be undertaken.
Læs mere Tjek på PubMedInfection, 10.07.2024
Tilføjet 10.07.2024
Abstract Pseudomonas aeruginosa is one of the most common nosocomial pathogens and part of the top emergent species associated with antimicrobial resistance that has become one of the greatest threat to public health in the twenty-first century. This bacterium is provided with a wide set of virulence factors that contribute to pathogenesis in acute and chronic infections. This review aims to summarize the impact of multidrug resistance on the virulence and fitness of P. aeruginosa. Although it is generally assumed that acquisition of resistant determinants is associated with a fitness cost, several studies support that resistance mutations may not be associated with a decrease in virulence and/or that certain compensatory mutations may allow multidrug resistance strains to recover their initial fitness. We discuss the interplay between resistance profiles and virulence from a microbiological perspective but also the clinical consequences in outcomes and the economic impact.
Læs mere Tjek på PubMedInfection, 10.07.2024
Tilføjet 10.07.2024
Infection, 10.07.2024
Tilføjet 10.07.2024
Abstract Immunosuppression constitutes a significant risk for community-acquired pneumonia (CAP). Nevertheless, specific causes of immunosuppression and their relevance for incidence, etiology and prognosis of CAP are insufficiently investigated. We conducted a population-based cohort study within a statutory health insurance in Germany from 2015 to 2018. CAP was retrieved by ICD-10-GM codes. Episodes of immunosuppression were identified by coded conditions (hematologic neoplasms, stem cell or organ transplantation, neutropenia, HIV, primary immunosuppressive syndromes) or treatments (immunosuppressants, antineoplastic drugs, systemic steroids). Endpoints were defined as occurrence of CAP (primary), hospitalization, 30-day mortality and CAP associated with rare pathogens. Our analysis utilized the Andersen-Gill model adjusted for sex, age, level of long-term care, vaccination status, community type and comorbidities. 942,008 individuals with 54,781 CAPs were included (hospitalization 55%, 30-day mortality 14.5%). 6% of individuals showed at least one episode of immunosuppression during the study period with systemic steroids (39.8%) and hematologic neoplasms (26.7%) being most common. Immunosuppression was recorded in 7.7% of CAPs. Besides classical risk factors such as age and level of long-term care, immunosuppressed patients were most prone to CAP (HR 2.4[2.3–2.5]) and consecutive death (HR 1.9[1.8–2.1]). Organ and stem cell transplantation (HR 3.2[2.6–4.0] and 2.8[2.1–3.7], respectively), HIV (HR 3.2[1.9–5.4]) and systemic steroids (> 20 mg prednisone daily dose equivalent (HR 2.7[2.4–3.1])) showed the highest risk for contracting CAP. CAP by rare pathogens was strongly associated with immunosuppression (HR 17.1[12.0–24.5]), especially HIV (HR 34.1[7.6–153]) and systemic steroids (HR 8.2[4.6–14.8]). Our study elucidates the relevance of particular immunosuppressive conditions including systemic steroids for occurrence and prognosis of CAP.
Læs mere Tjek på PubMedInfection, 10.07.2024
Tilføjet 10.07.2024
Abstract Background Nocardia often causes pulmonary infection among those with chronic pulmonary disease or immunocompromising conditions. Trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as first-line treatment, though little data exists regarding outcomes of different dosing regimens. Methods We performed a multicenter retrospective cohort study of adult patients with non-disseminated pulmonary nocardiosis initially treated with TMP-SMX monotherapy. Patients’ initial TMP-SMX dosing was categorized as high- (> 10 mg/kg/day), intermediate- (5–10 mg/kg/day) or low-dose (
Læs mere Tjek på PubMedInfection, 10.07.2024
Tilføjet 10.07.2024
Abstract Purpose Beta-lactam allergy (BLA) is associated with increased broad-spectrum antibiotic (Br-ABX) use and worse clinical outcomes. We evaluated our hospital-wide BLA protocol (BLA-P) that used following categories: intolerance, low-risk, and high-risk. Methods Hospitalized adult patients with listed BLA during 10/2021–12/2022 were eligible. Exclusions were critically ill, surgical, hospice or comfort care, or non-verbal patients. Assessment was counted each time a pharmacist evaluated BLA. Interventions were no further action (high-risk allergy, patient refusal, unstable clinical status), updated allergy label, or delabeled. Delabeling was done either based on antibiotic history (direct-delabeling), or via test-dose challenge for low-risk patients. Br-ABX usage was compared in the unique delabeled patients: the empiric antibiotic use 90 days post-delabeling versus pre-delabeling using McNemar test (SPSS). Results A total of 700 assessments in 631 patients were identified. 441 assessments in 377 patients (median 63 years-old, 41% male, 50% hematological cancer) met inclusion criteria. The assessments revealed 9% intolerance, 55% low-risk, 23% high-risk and 13% unknown reaction. Interventions resulted in no further action 7%, updated label 72%, and delabeling 21%. 65% of the delabeling was via direct-delabeling and 35% test-dose challenge. Among patients who received a test-dose challenge, 36/36(97%) had no documented allergic reactions, and 1/26(3%) developed a mild rash. The use of aztreonam (pre-delabeling 28% vs. post-delabeling 1.2%, p
Læs mere Tjek på PubMedLyu Xie, YanQin Wu, JinYong Jiang, HongNing Zhou
Journal of Medical Virology, 10.07.2024
Tilføjet 10.07.2024
Zhichao Liang, Changying Lin, Da Huo, Yang Yang, Zhaomin Feng, Shujuan Cui, Dan Wu, Zhenyong Ren, Dan Li, Lei Jia, Shuaibing Dong, Xiangfeng Dou, Yulan Sun, Zhiyong Gao, Renqing Li
Journal of Medical Virology, 10.07.2024
Tilføjet 10.07.2024
Xu Liu, Xi Liu, Chenyue Jin, Yuting Luo, Lianping Yang, Xinjiao Ning, Chao Zhuo, Fei Xiao
Clinical Microbiology and Infection, 10.07.2024
Tilføjet 10.07.2024
Prediction models help target patients at risk of multidrug-resistant organism (MDRO) colonisation or infection and could serve as tools informing clinical practices to prevent MDRO transmission and inappropriate empiric antibiotic therapy. However, limited evidence identifies which among the available models are of low risk of bias and suitable for clinical application.
Læs mere Tjek på PubMedMalte M. Tetens, Lars Haukali Omland, Nanna S. Andersen, Jette Bangsborg, Jacob Bodilsen, Ram B. Dessau, Svend Ellermann-Eriksen, Charlotte Sværke Jørgensen, Jens Kjølseth Møller, Alex Christian Yde Nielsen, Michael Pedersen, Kirstine K. Søgaard, Niels Obel, Anne-Mette Lebech
Clinical Microbiology and Infection, 10.07.2024
Tilføjet 10.07.2024
To identify diagnostic opportunities, we investigated healthcare-seeking behavior among patients with Lyme neuroborreliosis (LNB) within 28 weeks before diagnosis.
Læs mere Tjek på PubMedLeonard Leibovici, Julia Friedman
Clinical Microbiology and Infection, 10.07.2024
Tilføjet 10.07.2024
In 2023 we implemented a few major changes in CMI. We decided to invite editorial interns – people in early and mid-career – to join our Editorial Board. The purpose was twofold: to learn from people in training and mid-career on how we could better serve their needs; and to train a cadre of young people to serve as editors with CMI and other publications. In response to our call (1) we were pleasantly surprised to receive applications from 33 excellent candidates. Although we aimed at the beginning to invite one or two, we ended up inviting 7 outstanding people to join us as interns.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 10.07.2024
Tilføjet 10.07.2024
Abstract Adult-onset immunodeficiency with antibodies to interferon-γ (AOID with AIGA), is a rare, acquired immunodeficiency causing susceptibility to disseminated non-tuberculous mycobacteria and other intracellular opportunistic infections. The diagnosis depends on demonstrating the presence of endogenous anti-interferon-γ antibodies (AIGA) that suppress Th1 cell mediated immunity. Bioluminescent immunoassays are a newly emerging immunoassay format which utilise the action of bioluminescent enzymes on a substrate for specific analyte detection. In-short, detecting antibodies are conjugated with a bioluminescent enzyme. The detecting antibodies bind the analyte of interest and produce light (luminescence) after addition of a substrate. The purpose of this study was to evaluate two newly developed bioluminescent immunoassays using Lumit® (Promega) technology as a diagnostic test for AOID with AIGA. Specific aims included the clinical validation of a new inhibition bioluminescent immunoassay technique to detect AIGA which block detection of interferon-γ (IFN-γ) in-vitro and correlation of inhibition bioluminescent immunoassay results with AOID with AIGA disease status. Two bioluminescent inhibition immunoassays were developed. One which adapted an existing kit from Promega (Lumit® Human IFN-γ Immunoassay) and one which was developed in-house. 87 healthy controls and 48 patients with previously diagnosed AOID with AIGA were recruited and tested using these two methods. Results showed both bioluminescent inhibition immunoassays were able to clearly discriminate between AOID with AIGA patients and healthy controls. The mean inhibition percentage between patient groups correlated with disease activity. Both assays appeared to be more sensitive when compared to the existing inhibition ELISA.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 10.07.2024
Tilføjet 10.07.2024
Abstract Members of the T-cell immunoglobulin and mucin (TIM) family, which is crucial for T-cell function, are implicated in autoimmunity. TIM-1 and -3 play distinct roles in autoimmunity, with TIM-1 acting as a costimulatory molecule and TIM-3 regulating Th1 responses. We investigated the therapeutic potential of anti-TIM-1 (RMT1-10) and anti-TIM-3 (RMT3-23) antibodies in an autoimmune arthritis model. Zymosan A was used to induce arthritis in female SKG mice. The arthritis scores, histology, mRNA expression, cytokine levels, micro-CT, and flow cytometry results were obtained. The application of RMT1-10 reduced the arthritis scores, histological damage, and CD4+T cell infiltrations, and it suppressed interleukin (IL)-6 and -17A and reduced TIM-3 mRNA expressions. RMT3-23 also lowered arthritis severity, improved histology, and reduced serum levels of tumor necrosis factor (TNF)-α and IL-17A. RMT3-23 inhibited intracellular TNF-α and IL-6 and early apoptosis. An amelioration of autoimmune arthritis was achieved by blocking the TIM-1 and -3 signaling pathways via RMT1-10 and RMT3-23 administration, leading to a widespread decrease in inflammatory cytokines. Both antibodies exhibited therapeutic effects, suggesting TIM-1 and -3 as potential targets for rheumatoid arthritis.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 10.07.2024
Tilføjet 10.07.2024
Abstract Neutrophil extracellular traps released by neutrophils are web-like DNA structures adhered to granulin proteins with bactericidal activity and can be an important mechanism for preventing pathogen dissemination or eliminating microorganisms. However, they also play important roles in diseases of other systems, such as the central nervous system. We tracked the latest advances and performed a review based on published original and review articles related to neutrophil extracellular traps and neurological diseases. Generally, neutrophils barely penetrate the blood-brain barrier into the brain parenchyma, but when pathological changes such as infection, trauma, or neurodegeneration occur, neutrophils rapidly infiltrate the central nervous system to exert their defensive effects. However, neutrophils may adversely affect the host when they uncontrollably release neutrophil extracellular traps upon persistent neuroinflammation. This review focused on recent advances in understanding the mechanisms and effects of neutrophil extracellular traps release in neurological diseases, and we also discuss the role of molecules that regulate neutrophil extracellular traps release in anticipation of clinical applications in neurological diseases.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 10.07.2024
Tilføjet 10.07.2024
We read with great interest the recent publication by Preuß et al. on antibodies to beta tubulin 5 (anti-TBB5) in autoimmune liver diseases [1]. The group has previously done extensive work on the potential autoantigenic target of perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) in autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC), culminating in the likely identification of TBB5 as target of pANCA [2]. Based on the results however, the group now concludes that anti-TBB5 may be elevated in autoimmune liver diseases but is an unlikely target of pANCA.
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