Klebsiella pneumoniae (K. Mdivi-1 Dynamin inhibitor pneumoniae) is a causative agent of severe infections in humans. There is no publically available vaccine for K. pneumoniae infections yet. Here, using comprehensive immunoinformatics methods, T-cell-specific epitopes of four type 1 fimbriae antigens of K. pneumoniae were predicted and evaluated as potential vaccine candidates. Both CD8+ (class I) and CD4+ (class II) T-cell-specific epitopes were predicted and the epitopes similar to human proteome were excluded. Subsequently, the windows of class-II epitopes containing class-I epitopes were determined. The immunogenicity, IFN-γ production and population coverage were also estimated. Using the 3D structure of HLA and epitopes, molecular docking was carried out. Two best epitopes were selected for molecular dynamics studies. Our prediction and analyses resulted in the several dominant epitopes for each antigen. The docking results showed that all selected epitopes can bind to their restricted HLA molecules with high affinity. The molecular dynamics results indicated the stability of system with minimum possible deviation, suggesting the selected epitopes can be promising candidates for stably binding to HLA molecules. Altogether, our results suggest that the selected T-cell-specific epitopes of K. pneumoniae fimbriae antigens, particularly the two epitopes confirmed by molecular dynamics, can be applied for vaccine development. However, the in vitro and in vivo studies are required to authenticate the results of the present study. Communicated by Ramaswamy H. Sarma.Pluripotent stem cell-derived cerebral organoids have the potential to recapitulate the pathophysiology of in vivo human brain tissue, constituting a valuable resource for modelling brain disorders, including infectious diseases. Toxoplasma gondii, an intracellular protozoan parasite, infects most warm-blooded animals, including humans, causing toxoplasmosis. In immunodeficient patients and pregnant women, infection often results in severe central nervous system disease and fetal miscarriage. However, understanding the molecular pathophysiology of the disease has been challenging due to limited in vitro model systems. Here, we developed a new in vitro model system of T. gondii infection using human brain organoids. We observed that tachyzoites can infect human cerebral organoids and are transformed to bradyzoites and replicate in parasitophorous vacuoles to form cysts, indicating that the T. gondii asexual life cycle is efficiently simulated in the brain organoids. Transcriptomic analysis of T. gondii-infected organoids revealed the activation of the type I interferon immune response against infection. In addition, in brain organoids, T. gondii exhibited a changed transcriptome related to protozoan invasion and replication. This study shows cerebral organoids as physiologically relevant in vitro model systems useful for advancing the understanding of T. gondii infections and host interactions.Bacteria are the most common aetiological agents of community-acquired pneumonia (CAP) and use a variety of mechanisms to evade the host immune system. With the emerging antibiotic resistance, CAP-causing bacteria have now become resistant to most antibiotics. Consequently, significant morbimortality is attributed to CAP despite their varying rates depending on the clinical setting in which the patients being treated. Therefore, there is a pressing need for a safe and effective alternative or supplement to conventional antibiotics. Bacteriophages could be a ray of hope as they are specific in killing their host bacteria. Several bacteriophages had been identified that can efficiently parasitize bacteria related to CAP infection and have shown a promising protective effect. Thus, bacteriophages have shown immense possibilities against CAP inflicted by multidrug-resistant bacteria. This review provides an overview of common antibiotic-resistant CAP bacteria with a comprehensive summarization of the promising bacteriophage candidates for prospective phage therapy.Introduction. Patients presenting with symptoms of gastroesophageal reflux disease (GERD) are usually evaluated by gastroenterologists who perform the diagnostic workup and determine when to refer for surgical consideration. The multiple diagnostic studies can be overwhelming, and this leads to dropouts. In a rural setting, without gastroenterology services, the surgeon can diagnose GERD and perform antireflux procedures. This study aimed to assess the completion of the required diagnostic studies and progression to surgical intervention. Methods. This is a retrospective chart review of patients who presented with GERD symptoms between August 2015 and January 2018. Standardized workup included the upper gastrointestinal study and esophagogastroduodenoscopy with concomitant wireless pH placement. High-resolution impedance manometry and the gastric emptying scan were selectively utilized. Results. 429 patients were evaluated. Proton pump inhibitors were used by 82.2% of patients. The required diagnostic workup was completed by 92.7% of all patients. Nearly 75% were suitable candidates for antireflux surgery. Approximately 2/3 of these patients proceeded with antireflux surgery. Discussion. The lack of gastroenterology services in rural hospitals provides a unique opportunity for general surgeons to diagnose and treat GERD patients locally. This avoids fragmentation of care and enables the surgeon to evaluate the entire spectrum of GERD. This structured approach results in increased completion of multiple diagnostic studies. Moreover, surgical candidates are likely to proceed with surgical intervention. Conclusion. A surgical antireflux program with diagnostic and therapeutic capabilities results in increased completion of diagnostic workup and utilization of antireflux surgery.

Fevers following decannulation from veno-venous extracorporeal membrane oxygenation often trigger an infectious workup; however, the yield of this workup is unknown. We investigated the incidence of post-veno-venous extracorporeal membrane oxygenation decannulation fever as well as the incidence and nature of healthcare-associated infections in this population within 48 hours of decannulation.

All patients treated with veno-venous extracorporeal membrane oxygenation for acute respiratory failure who survived to decannulation between August 2014 and November 2018 were retrospectively reviewed. Trauma patients and bridge to lung transplant patients were excluded. The highest temperature and maximum white blood cell count in the 24 hours preceding and the 48 hours following decannulation were obtained. All culture data obtained in the 48 hours following decannulation were reviewed. Healthcare-associated infections included blood stream infections, ventilator-associated pneumonia, and urinary tract infections.