The etiology of community-acquired pneumonia requiring hospitalization in adults is evolving, in light of vaccine deployment and new diagnostic tests. This article defines pathogens potentially ...causing pneumonia. In a majority of cases, no pathogen was identified.
Pneumonia is a leading infectious cause of hospitalization and death among adults in the United States,
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with medical costs exceeding $10 billion in 2011.
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Routine administration of the pneumococcal conjugate vaccine in children has resulted in an overall reduction in the rate of invasive disease and pneumonia among adults, owing to herd immunity.
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The last U.S. population–based incidence estimates of hospitalization due to community-acquired pneumonia were made in the 1990s,
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before the availability of the pneumococcal conjugate vaccine and more sensitive molecular and antigen-based laboratory diagnostic tests. Thus, contemporary population-based etiologic studies involving U.S. adults with pneumonia are . . .
The delivery of nanoparticles into cells is important in therapeutic applications and in nanotoxicology. Nanoparticles are generally targeted to receptors on the surfaces of cells and internalized ...into endosomes by endocytosis, but the kinetics of the process and the way in which cell division redistributes the particles remain unclear. Here we show that the chance of success or failure of nanoparticle uptake and inheritance is random. Statistical analysis of nanoparticle-loaded endosomes indicates that particle capture is described by an over-dispersed Poisson probability distribution that is consistent with heterogeneous adsorption and internalization. Partitioning of nanoparticles in cell division is random and asymmetric, following a binomial distribution with mean probability of 0.52-0.72. These results show that cellular targeting of nanoparticles is inherently imprecise due to the randomness of nature at the molecular scale, and the statistical framework offers a way to predict nanoparticle dosage for therapy and for the study of nanotoxins.
More than 80% of patients with the refractory anemia with ring sideroblasts subtype of myelodysplastic syndrome (MDS) have mutations in Splicing Factor 3B, Subunit 1 (SF3B1). We generated a ...conditional knockin mouse model of the most common SF3B1 mutation, Sf3b1(K700E). Sf3b1(K700E) mice develop macrocytic anemia due to a terminal erythroid maturation defect, erythroid dysplasia, and long-term hematopoietic stem cell (LT-HSC) expansion. Sf3b1(K700E) myeloid progenitors and SF3B1-mutant MDS patient samples demonstrate aberrant 3' splice-site selection associated with increased nonsense-mediated decay. Tet2 loss cooperates with Sf3b1(K700E) to cause a more severe erythroid and LT-HSC phenotype. Furthermore, the spliceosome modulator, E7017, selectively kills SF3B1(K700E)-expressing cells. Thus, SF3B1(K700E) expression reflects the phenotype of the mutation in MDS and may be a therapeutic target in MDS.
Background. Prevalence of Staphylococcus aureus community-acquired pneumonia (CAP) and its clinical features remain incompletely understood, complicating empirical selection of antibiotics. Methods. ...Using a multicenter, prospective surveillance study of adults hospitalized with CAP, we calculated the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) among all CAP episodes. We compared the epidemiologic, radiographic, and clinical characteristics of S. aureus CAP (per respiratory or blood culture) with those of pneumococcal (per respiratory or blood culture or urine antigen) and all-cause non-S. aureus CAP using descriptive statistics. Results. Among 2259 adults hospitalized for CAP, 37 (1.6%) had S. aureus identified, including 15 (0.7%) with MRSA and 22 (1.0%) with MSSA; 115 (5.1%) had Streptococcus pneumoniae. Vancomycin or linezolid was administered to 674 (29.8%) patients within the first 3 days of hospitalization. Chronic hemodialysis use was more common among patients with MRSA (20.0%) than pneumococcal (2.6%) and all-cause non-S. aureus (3.7%) CAP. Otherwise, clinical features at admission were similar, including concurrent influenza infection, hemoptysis, multilobar infiltrates, and prehospital antibiotics. Patients with MRSA CAP had more severe clinical outcomes than those with pneumococcal CAP, including intensive care unit admission (86.7% vs 34.8%) and in-patient mortality (13.3% vs 4.4%). Conclusions. Despite very low prevalence of S. aureus and, specifically, MRSA, nearly one-third of adults hospitalized with CAP received anti-MRSA antibiotics. The clinical presentation of MRSA CAP overlapped substantially with pneumococcal CAP, highlighting the challenge of accurately targeting empirical anti-MRSA antibiotics with currently available clinical tools and the need for new diagnostic strategies.
Amide proton transfer‐weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different ...institutes, and there are no agreed‐on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi‐center trials in larger patient cohorts and, ultimately, routine clinical use.
Plants and their pathogens coevolve locally. Previous investigations of one host–one pathogen systems have demonstrated that natural selection favors pathogen genotypes that are virulent on a broad ...range of host genotypes. In the present study, we examine a system consisting of one pathogen species that infects three host species in the morning glory genus Ipomoea. We show that many pathogen genotypes can infect two or three of the host species when tested on plants from nonlocal communities. By contrast, pathogen genotypes are highly host-specific, infecting only one host species, when tested on host species from the local community. This pattern indicates that within-community evolution narrows the host breadth of pathogen genotypes. Possible evolutionary mechanisms include direct selection for narrow host breadth due to costs of virulence and evolution of ipomoea resistance in the host species.
Background Predicting the need for intensive care among adults with community-acquired pneumonia (CAP) remains challenging. Methods Using a multicenter prospective cohort study of adults hospitalized ...with CAP, we evaluated the association of serum procalcitonin (PCT) concentration at hospital presentation with the need for invasive respiratory or vasopressor support (IRVS), or both, within 72 h. Logistic regression was used to model this association, with results reported as the estimated risk of IRVS for a given PCT concentration. We also assessed whether the addition of PCT changed the performance of established pneumonia severity scores, including the pneumonia severity index and the American Thoracic Society minor criteria, for prediction of IRVS. Results Of 1,770 enrolled patients, 115 required IRVS (6.5%). Using the logistic regression model, PCT concentration had a strong association with IRVS risk. Undetectable PCT (< 0.05 ng/mL) was associated with a 4% (95% CI, 3.1%-5.1%) risk of IRVS. For concentrations < 10 ng/mL, PCT had an approximate linear association with IRVS risk: for each 1 ng/mL increase in PCT, there was a 1% to 2% absolute increase in the risk of IRVS. With a PCT concentration of 10 ng/mL, the risk of IRVS was 22.4% (95% CI, 16.3%-30.1%) and remained relatively constant for all concentrations > 10 ng/mL. When added to each pneumonia severity score, PCT contributed significant additional risk information for the prediction of IRVS. Conclusions Serum PCT concentration was strongly associated with the risk of requiring IRVS among adults hospitalized with CAP and is potentially useful for guiding decisions about ICU admission.
The goals of this study were to determine the current and projected supply in 2030 of contributors to emergency care, including emergency residency-trained and board-certified physicians, other ...physicians, nurse practitioners, and physician assistants. In addition, this study was designed to determine the current and projected demand for residency-trained, board-certified emergency physicians.
To forecast future workforce supply and demand, sources of existing data were used, assumptions based on past and potential future trends were determined, and a sensitivity analysis was conducted to determine how the final forecast would be subject to variance in the baseline inputs and assumptions. Methods included: (1) estimates of the baseline workforce supply of physicians, nurse practitioners, and physician assistants; (2) estimates of future changes in the raw numbers of persons entering and leaving that workforce; (3) estimates of the productivity of the workforce; and (4) estimates of the demand for emergency care services. The methodology assumes supply equals demand in the base year and estimates the change between the base year and 2030; it then compares supply and demand in 2030 under different scenarios.
The task force consensus was that the most likely future scenario is described by: 2% annual graduate medical education growth, 3% annual emergency physician attrition, 20% encounters seen by a nurse practitioner or physician assistant, and 11% increase in emergency department visits relative to 2018. This scenario would result in a surplus of 7,845 emergency physicians in 2030.
The specialty of emergency medicine is facing the likely oversupply of emergency physicians in 2030. The factors leading to this include the increasing supply of and changing demand for emergency physicians. An organized, collective approach to a balanced workforce by the specialty of emergency medicine is imperative.
We examined the genetic basis of resistance to the rust pathogen Coleosporium ipomoea in three host species: Ipomoea purpurea, I. hederacea, and I. coccinea (Convolvulaceae). In crosses between ...resistant and susceptible individuals, second-generation selfed offspring segregated in ratios that did not differ statistically from the 3:1 ratio indicative of single-gene resistance with the resistant allele dominant. One out of three crosses between resistant individuals from two different populations revealed that resistance loci differed in the two populations, as evidenced by the production of susceptible individuals among the S(2) generation. These results suggest that gene-for-gene interactions contribute substantially to the dynamics of coevolution in this natural pathosystem. They also suggest that evolution of resistance to the same pathogen strain may involve different loci in different Ipomoea populations.
Children's early language environments are related to later development. Little is known about this association in siblings of children with autism spectrum disorder (ASD), who often experience ...language delays or have ASD. Fifty‐nine 9‐month‐old infants at high or low familial risk for ASD contributed full‐day in‐home language recordings. High‐risk infants produced more vocalizations than low‐risk peers; conversational turns and adult words did not differ by group. Vocalization differences were driven by a subgroup of “hypervocal” infants. Despite more vocalizations overall, these infants engaged in less social babbling during a standardized clinic assessment, and they experienced fewer conversational turns relative to their rate of vocalizations. Two ways in which these individual and environmental differences may relate to subsequent development are discussed.
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