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IScience Jul 2023The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties....
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for effective anti-SARS-CoV-2 agents against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production, and potential for delivery via inhalation. Here, we characterize the receptor binding domain (RBD)-specific nanobody W25 and show superior neutralization activity toward Omicron sub-lineages in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse W25 for further clinical development.
PubMed: 37361875
DOI: 10.1016/j.isci.2023.107085 -
Environmental Technology Jun 2024Diesel degradation and bacterial growth were investigated in soil, marine water, and freshwater ecosystems using IITG19, IITG20, and their mixed culture. Both bacteria...
Diesel degradation and bacterial growth were investigated in soil, marine water, and freshwater ecosystems using IITG19, IITG20, and their mixed culture. Both bacteria were found to be effective in all three ecosystems, with the best degradation occurring in freshwater. IITG19 showed higher degradation (59%, 62%, and 76%) than (31%, 57%, and 67%) in soil, marine water, and freshwater, respectively. Alkanes showed higher degradation than naphthenes and aromatics for both strains. The mixed culture showed higher diesel degradation efficiency than individual strains in all ecosystems. The overall degradation was similar in soil and marine water (66%), while freshwater showed the highest degradation of 81%. In the presence of the mixed culture, the degradation of alkanes was more than 90%. Bacterial growth was highest in freshwater and lowest in soil for both bacteria and the mixed culture. Metabolite analysis confirmed alcoholic degradation for alkanes and cyclo-alcoholic degradation for naphthenes. The degradation rate for mixed culture was higher than that of both the individual strains. The mixed culture had highest degradation rate constant in freshwater at 0.11 day followed by that in marine ecosystem at 0.078 day. The rate constant was lowest for soil ecosystem at 0.066 day Thus the mixed culture showed effectiveness in all three ecosystems, with its highest effectiveness observed in the freshwater ecosystem.
PubMed: 38837716
DOI: 10.1080/09593330.2024.2361171 -
International Journal of Antimicrobial... May 2024The ESCPM group (Enterobacter species including Klebsiella aerogenes - formerly Enterobacter aerogenes, Serratia species, Citrobacter freundii complex, Providencia... (Observational Study)
Observational Study
INTRODUCTION
The ESCPM group (Enterobacter species including Klebsiella aerogenes - formerly Enterobacter aerogenes, Serratia species, Citrobacter freundii complex, Providencia species and Morganella morganii) has not yet been incorporated into systematic surveillance programs.
METHODS
We conducted a multicentre retrospective observational study analysing all ESCPM strains isolated from blood cultures in 27 European hospitals over a 3-year period (2020-2022). Diagnostic approach, epidemiology, and antimicrobial susceptibility were investigated.
RESULTS
Our study comprised 6,774 ESCPM isolates. MALDI-TOF coupled to mass spectrometry was the predominant technique for bacterial identification. Susceptibility to new β-lactam/β-lactamase inhibitor combinations and confirmation of AmpC overproduction were routinely tested in 33.3% and 29.6% of the centres, respectively. The most prevalent species were E. cloacae complex (44.8%) and S. marcescens (22.7%). Overall, third-generation cephalosporins (3GC), combined third- and fourth-generation cephalosporins (3GC + 4GC) and carbapenems resistance phenotypes were observed in 15.7%, 4.6%, and 9.5% of the isolates, respectively. AmpC overproduction was the most prevalent resistance mechanism detected (15.8%). Among carbapenemase-producers, carbapenemase type was provided in 44.4% of the isolates, VIM- (22.9%) and OXA-48-enzyme (16%) being the most frequently detected. E. cloacae complex, K. aerogenes and Providencia species exhibited the most notable cumulative antimicrobial resistance profiles, with the former displaying 3GC, combined 3GC + 4GC and carbapenems resistance phenotypes in 15.2%, 7.4%, and 12.8% of the isolates, respectively. K. aerogenes showed the highest rate of both 3GC resistant phenotype (29.8%) and AmpC overproduction (32.1%), while Providencia species those of both carbapenems resistance phenotype (42.7%) and carbapenemase production (29.4%). ESCPM isolates exhibiting both 3GC and combined 3GC + 4GC resistance phenotypes displayed high susceptibility to ceftazidime/avibactam (98.2% and 95.7%, respectively) and colistin (90.3% and 90.7%, respectively). Colistin emerged as the most active drug against ESCPM species (except those intrinsically resistant) displaying both carbapenems resistance phenotype (85.8%) and carbapenemase production (97.8%).
CONCLUSIONS
This study presented a current analysis of ESCPM species epidemiology in Europe, providing insights to inform current antibiotic treatments and guide strategies for antimicrobial stewardship and diagnostics.
Topics: Humans; Bacterial Proteins; Europe; beta-Lactamases; Retrospective Studies; Enterobacteriaceae Infections; Anti-Bacterial Agents; Microbial Sensitivity Tests; Enterobacteriaceae; Hospitals; beta-Lactamase Inhibitors; Drug Resistance, Multiple, Bacterial
PubMed: 38367844
DOI: 10.1016/j.ijantimicag.2024.107115 -
Heliyon Jul 2023Achieving sustainability and resilience depends on the conciliation of environmental, social, and economic issues integrated into a long-term perspective to ensure...
Achieving sustainability and resilience depends on the conciliation of environmental, social, and economic issues integrated into a long-term perspective to ensure communities flourish. Many nations are transitioning toward both objectives, while at the same time addressing structural concerns that have not allowed them to look after the environment in the past. Chile is one of these nations dealing with such challenges within a particular administrative context, an increasing environmental awareness, and a set of unique and complex geophysical boundaries that impose a plethora of hazards for cities, ecosystems, and human health. This paper presents recent accomplishments and gaps, mostly from an environmental perspective, on issues related to air pollution, the urban water cycle, and soil contamination, in the path being followed by Chile toward urban sustainability and resilience. The focus is on the bonds between cities and their geophysical context, as well as the relationships between environmental issues, the built environment, and public health. The description and diagnosis are illustrated using two cities as case studies, Temuco and Copiapó, whose socioeconomic, geographical, and environmental attributes differ considerably. Particulate matter pollution produced by the residential sector, drinking water availability, wastewater treatment, stormwater management, and soil contamination from the mining industry are discussed for these cities. Overall, the case studies highlight how tackling these issues requires coordinated actions in multiple areas, including regulatory, information, and financial incentive measures. Finally, the policy analysis discusses frameworks and opportunities for Chilean cities, which may be of interest when conceiving transitional paths toward sustainability and resilience for other cities elsewhere.
PubMed: 37519708
DOI: 10.1016/j.heliyon.2023.e18191 -
Life (Basel, Switzerland) Aug 2023Catheter ablation has been shown to be more effective at maintaining sinus rhythm and improving quality of life when compared to antiarrhythmic drugs. Radiofrequency and... (Review)
Review
Catheter ablation has been shown to be more effective at maintaining sinus rhythm and improving quality of life when compared to antiarrhythmic drugs. Radiofrequency and cryoablation are two effective methods. However, catheter-only ablation strategies have not consistently produced high success rates in treating longstanding and persistent AF patients. The emerging treatment of choice for such cases is hybrid ablation, which involves a multidisciplinary and minimally invasive approach to achieve surgical ablation of the direct posterior left atrial wall in combination with endocardial catheter ablation. Studies have shown promising results for the hybrid approach when compared with catheter ablation alone, but it is not without risks. Large and randomised studies are necessary to further evaluate these strategies for managing AF.
PubMed: 37629641
DOI: 10.3390/life13081784 -
European Journal of Nuclear Medicine... May 2024Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis. Ga-labeled FAP ligands exhibited highly promising results due...
UNLABELLED
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis. Ga-labeled FAP ligands exhibited highly promising results due to the crucial role of activated fibroblasts in fibrosis imaging of the lung. However, F-labeled FAP ligands might provide qualitatively much higher imaging results with accompanying economic benefits due to large-scale production. Thus, we sought to investigate the potential of [F]FAPI-74 prospectively in a small patient cohort.
METHODS
Eight patients underwent both [F]FAPI-74-PET/CT and HRCT scans and were then compared with a control group without any fibrosing pulmonary disease. The tracer uptake of fibrotic lung areas was analyzed in synopsis with radiological and clinical parameters.
RESULTS
We observed a positive correlation between the fibrotic active volume, the Hounsfield scale, as well as the vital and diffusing capacity of the lung.
CONCLUSION
The initial results confirm our assumption that [F]FAPI-74 offers a viable non-invasive assessment method for pulmonary fibrotic changes in patients with IPF.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Positron Emission Tomography Computed Tomography; Male; Female; Aged; Middle Aged; Lung
PubMed: 38117298
DOI: 10.1007/s00259-023-06564-y -
Microbiology Spectrum Aug 2023Changes in diet and environment can lead to acute diarrhea in companion animals, but the composition and interactions of the gut microbiome during acute diarrhea remain...
Changes in diet and environment can lead to acute diarrhea in companion animals, but the composition and interactions of the gut microbiome during acute diarrhea remain unclear. In this multicenter case-control study, we investigated the relationship between intestinal flora and acute diarrhea in two breeds of cats. Acutely diarrheic American Shorthair (MD, = 12) and British Shorthair (BD, = 12) and healthy American Shorthair (MH, = 12) and British Shorthair (BH, = 12) cats were recruited. Gut microbial 16S rRNA sequencing, metagenomic sequencing, and untargeted metabolomic analysis were performed. We observed significant differences in beta-diversity (Adonis, < 0.05) across breeds and disease state cohorts. Profound differences in gut microbial structure and function were found between the two cat breeds. In comparison to healthy British Shorthair cats, , , and were enriched while , , and were reduced in American Shorthair cats. In the case-control cohort, cats with acute diarrhea exhibited an increased abundance of , , and Prevotella copri and a decreased abundance of , , and (both MD and BD cats, < 0.05). Metabolomic analysis identified significant changes in the BD intestine, affecting 45 metabolic pathways. Moreover, using a random forest classifier, we successfully predicted the occurrence of acute diarrhea with an area under the curve of 0.95. Our findings indicate a distinct gut microbiome profile that is associated with the presence of acute diarrhea in cats. However, further investigations using larger cohorts of cats with diverse conditions are required to validate and extend these findings. Acute diarrhea is common in cats, and our understanding of the gut microbiome variations across breeds and disease states remains unclear. We investigated the gut microbiome of two cat breeds (British Shorthair and American Shorthair) with acute diarrhea. Our study revealed significant effects of breeds and disease states on the structure and function of the gut microbiota in cats. These findings emphasize the need to consider breed-related factors in animal nutrition and research models. Additionally, we observed an altered gut metabolome in cats with acute diarrhea, closely linked to changes in bacterial genera. We identified a panel of microbial biomarkers with high diagnostic accuracy for feline acute diarrhea. These findings provide novel insights into the diagnosis, classification, and treatment of feline gastrointestinal diseases.
Topics: Cats; Animals; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Case-Control Studies; Feces; Diarrhea; Firmicutes
PubMed: 37428087
DOI: 10.1128/spectrum.00590-23 -
Journal of Clinical Oncology : Official... Jun 2024JCO We report 3-year efficacy and safety results from the phase III CheckMate 649 trial. Patients with previously untreated advanced or metastatic gastroesophageal... (Randomized Controlled Trial)
Randomized Controlled Trial
First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial.
JCO We report 3-year efficacy and safety results from the phase III CheckMate 649 trial. Patients with previously untreated advanced or metastatic gastroesophageal adenocarcinoma were randomly assigned to nivolumab plus chemotherapy or chemotherapy. Primary end points were overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) in patients whose tumors expressed PD-L1 combined positive score (CPS) ≥5. With 36.2-month minimum follow-up, for patients with PD-L1 CPS ≥5, the OS hazard ratio (HR) for nivolumab plus chemotherapy versus chemotherapy was 0.70 (95% CI, 0.61 to 0.81); 21% versus 10% of patients were alive at 36 months, respectively; the PFS HR was 0.70 (95% CI, 0.60 to 0.81); 36-month PFS rates were 13% versus 8%, respectively. The objective response rate (ORR) per BICR was 60% (95% CI, 55 to 65) with nivolumab plus chemotherapy versus 45% (95% CI, 40 to 50) with chemotherapy; median duration of response was 9.6 months (95% CI, 8.2 to 12.4) versus 7.0 months (95% CI, 5.6 to 7.9), respectively. Nivolumab plus chemotherapy also continued to show improvement in OS, PFS, and ORR versus chemotherapy in the overall population. Adding nivolumab to chemotherapy maintained clinically meaningful long-term survival benefit versus chemotherapy alone, with an acceptable safety profile, supporting the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastroesophageal adenocarcinoma.
Topics: Humans; Esophageal Neoplasms; Adenocarcinoma; Stomach Neoplasms; Nivolumab; Esophagogastric Junction; Antineoplastic Combined Chemotherapy Protocols; Male; Follow-Up Studies; Female; Aged; Middle Aged; Progression-Free Survival; Adult
PubMed: 38382001
DOI: 10.1200/JCO.23.01601 -
MedRxiv : the Preprint Server For... Nov 2023Metabolomic age models have been proposed for the study of biological aging, however they have not been widely validated. We aimed to assess the performance of newly...
Metabolomic age models have been proposed for the study of biological aging, however they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. 98 metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈ 31,000 individuals, age range 24-86 years). We used non-linear and penalised regression to model CA and time to all-cause mortality. We examined associations of four new and two previously published metabolomic age models, with ageing risk factors and phenotypes. Within the UK Biobank (N≈ 102,000), we tested prediction of CA, incident disease (cardiovascular disease (CVD), type-2 diabetes mellitus, cancer, dementia, chronic obstructive pulmonary disease) and all-cause mortality. Cross-validated Pearson's between metabolomic age models and CA ranged between 0.47-0.65 in the training set (mean absolute error: 8-9 years). Metabolomic age models, adjusted for CA, were associated with C-reactive protein, and inversely associated with glomerular filtration rate. Positively associated risk factors included obesity, diabetes, smoking, and physical inactivity. In UK Biobank, correlations of metabolomic age with chronological age were modest ( = 0.29-0.33), yet all metabolomic model scores predicted mortality (hazard ratios of 1.01 to 1.06 / metabolomic age year) and CVD, after adjustment for CA. While metabolomic age models were only moderately associated with CA in an independent population, they provided additional prediction of morbidity and mortality over CA itself, suggesting their wider applicability.
PubMed: 37986811
DOI: 10.1101/2023.11.07.23298200 -
BMC Microbiology Oct 2023This study aimed to investigate the clinical infection characteristics and analyze the resistance gene carrying status of carbapenem-resistant Providencia rettgeri via...
OBJECTIVE
This study aimed to investigate the clinical infection characteristics and analyze the resistance gene carrying status of carbapenem-resistant Providencia rettgeri via whole genome sequencing (WGS).
METHODS
Carbapenem-resistant P. rettgeri were collected from clinical patients between January 2020 and December 2021, and their susceptibility to 19 antimicrobial drugs was determined using the VITEK 2 Compact system and Kirby-Bauer (KB) disk diffusion method. The Illumina platform was used to perform WGS of the P. rettgeri isolates, and the resistance genes carried by the Carbapenem-resistant P. rettgeri strains were detected via ABRicate software. The phylogenetic tree was constructed by thirty-four strains including twenty-eight strains downloaded from NCBI database and the carbapenem-resistant six P. rettgeri strains in this study. Which based on genomic single nucleotide polymorphism (SNP) to understand the affinities of the carbapenem-resistant P. rettgeri strains.
RESULTS
Six carbapenem-resistant P. rettgeri strains were isolated from five different clinical departments using the blood, urine, sputum, and secretion specimens. These infected patients are middle-aged and elderly people with a history of severe trauma, tumors, hypertension, and various other underlying diseases, and invasive procedures. Antimicrobial sensitivity testing showed that all strains presented resistance to ampicillin-sulbactam, ceftazidime, ciprofloxacin, levofloxacin, and ertapenem, whereas they exhibited full susceptibility to cefepime and amikacin. Most strains demonstrated high resistance to β-lactams, aminoglycosides, and sulfonamides. Thirty-five resistance genes were identified by ABRicate. All carbapenem-resistant P. rettgeri strains carried aminoglycoside, fluoroquinolone, chloramphenicol, rifampicin, sulfonamide, and β-lactam resistance genes, and most importantly, all strains possessed the carbapenem resistance gene bla. The six P. rettgeri strains in this study and the 28 carbapenem-resistant P. rettgeri strains from the NCBI database were divided into four evolutionary groups. The WF3643, WF3849, WF3822, and WF3821 strains in this study were in the same evolutionary group (clade A), while the closely related WF3099 and WF3279 strains were in different evolutionary groups (clade B and clade D), respectively. The WF3099 strain was distantly related to the other five strains.
CONCLUSION
Carbapenem-resistant P. rettgeri strains were mostly isolated from middle-aged and older patients with a history of surgery or serious underlying diseases, and they were found to cause multisystem infections. All Carbapenem-resistant P. rettgeri strains in this study carried bla and multiple antimicrobial drug resistance genes. Furthermore, the P. rettgeri strains in this study were closely related, suggesting the possibility of nosocomial infections. Therefore, our study highlights the need for research on P. rettgeri to control the spread of these nosocomial infections.
Topics: Middle Aged; Aged; Humans; beta-Lactamases; Phylogeny; Anti-Bacterial Agents; Carbapenems; Aminoglycosides; Whole Genome Sequencing; Cross Infection; Microbial Sensitivity Tests
PubMed: 37789331
DOI: 10.1186/s12866-023-03032-3