Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal ...cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism.
In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR.
The median age of our cohort was 73·5 years (range 42–84; IQR 67·5–77·25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue.
The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination.
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Lower respiratory infections remain one of the top global causes of death and the emergence of new diseases continues to be a concern. In the first two decades of the 21st century, we have born ...witness to the emergence of newly recognized coronaviruses that have rapidly spread around the globe, including severe acute respiratory syndrome virus (SARS) and Middle Eastern respiratory syndrome virus (MERS). We have also experienced the emergence of a novel H1N1 pandemic influenza strain in 2009 that caused substantial morbidity and mortality around the world and has transitioned into a seasonal strain. Although we perhaps most frequently think of viruses when discussing emerging respiratory infections, bacteria have not been left out of the mix, as we have witnessed an increase in the number of infections from Legionella spp. since the organisms’ initial discovery in 1976. Here, we explore the basic epidemiology, clinical presentation, histopathology, and clinical laboratory diagnosis of these four pathogens and emphasize themes in humans’ evolving relationship with our natural environment that have contributed to the infectious burden. Histology alone is rarely diagnostic for these infections, but has been crucial to bettering our understanding of these diseases. Together, we rely on the diagnostic acumen of pathologists to identify the clinicopathologic features that raise the suspicion of these diseases and lead to the early control of the spread in our populations.
•This is the largest study of mpox NAAT testing in pediatric patients.•63.1% (12/19) of mpox cases occurred in the < 1-year-old or 17-year-old age groups.•Pediatric specimens are more frequently ...collected from females and non-genital sites.•The positive predictive value of MPXV detection in children was 90.5%.
Pediatric mpox cases comprise less than 0.3% of the total cases reported in the United States during the global 2022 outbreak. As a result, relatively little is known about the epidemiology or performance characteristics of clinical testing in this group.
We retrospectively extracted and analyzed results for pediatric mpox specimens tested at a national reference laboratory from July to December 2022.
During our study period 13.4% (2,063/15,385) of specimens were from individuals <18 years of age. The positivity rate of pediatric specimens was significantly lower than in adults (1.3% vs 22.3%). The pediatric cohort also consisted of a higher percentage of females (42.7% vs 31.0%) and lower percentage of specimens from genital sources (9.0% vs 19.7%) as compared to adults. In children, specimens were most frequently collected from 1-year-olds (10.1%) and least frequently from 11-year-olds (3.5%). Positivity rates were disproportionately elevated in the less than 1-year-old and 17-year-old age groups (7.8% and 6.4%, respectively). Ct values of positive cases were not statistically different between pediatric and adult cohorts (25.2 vs 22.2, p>0.05). When all pediatric cases with an initial positive mpox result were examined, 5/26 were classified as inconclusive and 2/26 were determined to be false positives. The positive predictive value of monkeypox virus detection was 90.5% (95% CI: 70.4–97.4%) in children.
These results highlight important differences between pediatric and adult mpox populations and reinforce the need for clinical correlation when reporting positive results from a low prevalence population.
While the practice of viral culture has largely been replaced by nucleic acid amplification tests, circumstances still exist in which the availability of viral culture will allow for the diagnosis of ...infections not included in a provider's differential diagnosis. Here, we examine the cytopathic effects (CPE) and clinical data associated with 18 cases of monkeypox virus (MPXV) isolated from 19 clinical samples submitted for viral culture. During the study period, a total of 3,468 viral cultures were performed with herpes simplex virus (HSV) most commonly isolated (646/3,468; 18.6%), followed by MPXV (19/3,468; 0.6%) and varicella-zoster virus (VZV) (12/3,468; 0.4%). Most MPXV-positive samples were obtained from males (14/19) and taken from genital (7/19) or rectal lesions (5/19). Cycle threshold values of tested samples ranged from 15.3 to 29.0. Growth of MPXV in cell culture was rapid, yielding detectable CPE at a median of 2 days (range: 1 to 4) often with >50% of the monolayer affected in RMK, BGM, A549, and MRC-5 cell lines. As clinical features of MPXV, HSV, and VZV lesions may overlap, CPE patterns were compared between viruses. HSV CPE developed in a similar time frame (median: 2 days, range: 1 to 7) but was more often negative in RMK cells relative to MPXV. VZV grew more slowly (median: 9 days, range: 5 to 11) and demonstrated CPE affecting ≤25% of cell monolayers when positive. Viral culture remains an important tool for the detection of rare or emerging viral pathogens, particularly when high viral load specimens are easily obtained.
Abstract
Leishmaniasis is a vector-borne infection caused by kinetoplastid protozoans in the genera Leishmania and Endotrypanum. The disease occurs worldwide in the tropics and subtropics and can be ...particularly burdensome in resource-limited settings. Diseases caused by leishmaniasis range in severity from mild cutaneous lesions to life-threatening visceral and disfiguring mucocutaneous illnesses. Rapid and accurate diagnosis is needed to ensure proper clinical management of patients afflicted with this disease. Complicating matters of diagnosis and treatment are the diversity of species within these 2 genera and the variable specificity of diagnostic assays. This mini-review provides laboratory professionals with an overview of Leishmania epidemiology, biology, pathogenesis, clinical presentations, and treatments with additional emphasis placed on the nuances involved in diagnosis.
Relative to the atmosphere, much of the aerobic ocean is supersaturated with methane; however, the source of this important greenhouse gas remains enigmatic. Catabolism of methylphosphonic acid by ...phosphorus-starved marine microbes, with concomitant release of methane, has been suggested to explain this phenomenon, yet methylphosphonate is not a known natural product, nor has it been detected in natural systems. Further, its synthesis from known natural products would require unknown biochemistry. Here we show that the marine archaeon Nitrosopumilus maritimus encodes a pathway for methylphosphonate biosynthesis and that it produces cell-associated methylphosphonate esters. The abundance of a key gene in this pathway in metagenomic data sets suggests that methylphosphonate biosynthesis is relatively common in marine microbes, providing a plausible explanation for the methane paradox.
Agriculture comprises the largest global land use, makes it a leading cause of habitat loss. It is therefore critical to identify how to best construct agricultural systems that can simultaneously ...provide food and other ecosystem services. This challenge requires that we determine how to maximize win‐win relationships and minimize trade‐offs between services. Through meta‐analysis, we tested whether within‐field crop diversification (polyculture) can lead to win‐win relationships between two ecosystem services: yield of a focal crop species and biocontrol of crop pests. We selected only studies that recorded both services (N = 26 studies; 301 observations), allowing us to better determine the underlying mechanisms of our principal findings. We calculated log‐response ratios for both ecosystem services in mono‐ and polycultures. We found win‐win relationships between per‐plant yield of the primary crop and biocontrol in polyculture systems that minimized intraspecific competition via substitutive planting. Additionally, we found beneficial effects on biocontrol with no difference in per‐unit area yield of the primary crop in polyculture fields at high cropping densities (additive planting) where legumes were used as the secondary crop. These results suggest that there is a strong potential for win‐win relationships between biocontrol and per‐unit area yield under certain scenarios. Our findings were consistent across geographical regions and by type of primary crop. We did not find evidence that biocontrol had an effect on yield, but rather, both were independently affected by polycultural cropping. Synthesis and applications. We show that well‐designed polycultures can produce win‐win outcomes between per‐plant, and potentially per‐unit area, primary crop yield and biocontrol. Biocontrol services are consistently enhanced in polycultures, so polyculture management that focuses on yield optimization is likely to be the best strategy for maximizing both services. In doing so, we suggest that practitioners utilize polycultures that decrease plant–plant competition through a substitution of relatively large quantities of the primary crop for compatibly harvestable secondary crops. Additionally, if planting at high cropping densities, it is important that legumes be the secondary crop.
Control of protein homeostasis is fundamental to the health and longevity of all organisms. Because the rate of protein synthesis by ribosomes is a central control point in this process, regulation, ...and maintenance of ribosome function could have amplified importance in the overall regulatory circuit. Indeed, ribosomal defects are commonly associated with loss of protein homeostasis, aging, and disease (1–4), whereas improved protein homeostasis, implying optimal ribosomal function, is associated with disease resistance and increased lifespan (5–7). To maintain a high-quality ribosome population within the cell, dysfunctional ribosomes are targeted for autophagic degradation. It is not known if complete degradation is the only mechanism for eukaryotic ribosome maintenance or if they might also be repaired by replacement of defective components. We used stable-isotope feeding and protein mass spectrometry to measure the kinetics of turnover of ribosomal RNA (rRNA) and 71 ribosomal proteins (r-proteins) in mice. The results indicate that exchange of individual proteins and whole ribosome degradation both contribute to ribosome maintenance in vivo. In general, peripheral r-proteins and those with more direct roles in peptide-bond formation are replaced multiple times during the lifespan of the assembled structure, presumably by exchange with a free cytoplasmic pool, whereas the majority of r-proteins are stably incorporated for the lifetime of the ribosome. Dietary signals impact the rates of both new ribosome assembly and component exchange. Signal-specific modulation of ribosomal repair and degradation could provide a mechanistic link in the frequently observed associations among diminished rates of protein synthesis, increased autophagy, and greater longevity (5, 6, 8, 9).
As information technology (IT) proliferates across functional units, manufacturers that lack a coherent strategy for integrating, standardizing and leveraging their IT resources and capabilities are ...more likely to end up with fragmented systems that do not properly support business processes and hinder performance. One strategic approach to facilitating standardization and integration among IT resources is enterprise architecture (EA). As the representation of an enterprise's business processes and IT systems, EA underpins decisions relating to data, applications, IT infrastructure (technical and human), and management responsibilities in order to inform business strategies that enable organizations to accomplish their business objectives. In this research, we leverage competence-based theory to introduce EA strategic orientation and EA assimilation as dynamic and operational capabilities, respectively. Data collected from 190 manufacturers and seemingly unrelated regression are used to test hypotheses related to a nomological network consisting of EA strategic orientation, EA assimilation, agility and firm performance. The findings suggest that EA-based capabilities can enhance agility, and indirectly increase firm performance. As the first study to assess the value of EA from a non-IT-centric perspective, this work serves as a pivot point for examining the reach and range of EAbased capabilities, particularly in operations management. The findings provide operations and IT managers with evidence of how enterprise IT initiatives are ultimately linked to firm performance by way of EA-based capabilities.
The mpox pandemic necessitated the rapid development of clinical assays for monkeypox virus detection. While the majority of mpox specimens have high viral loads with corresponding early cycle ...threshold (CT) values, reports have indicated some specimens with late CT values can represent false positive results. To mitigate this risk, the Centers for Disease Control and Prevention (CDC) published an advisory recommending repeat testing of all specimens with CT values ≥34. However, limited experimental data were available to support this specific cutoff. In this study, we examine whether a more conservative approach in which all specimens with CT values ≥29 are repeated would improve the detection of potential false positive results. Compared to the CDC algorithm, our approach identified an additional 20% (5/25) of potential false positive results. To assess the impact of this cutoff on laboratory workload, we modeled the expected increase in test volume and turnaround time (TAT) relative to the CDC method. Using a lower repeat threshold, test volume increased by 0.7% while mean TAT increased by less than 15 minutes. Overall, a lower threshold than recommended by the CDC for repeating late CT mpox specimens may reduce the number of false positives reported while minimally impacting testing volume and TAT.
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