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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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The dominant reservoirs of elemental nitrogen in protoplanetary disks have not yet been observationally identified. Likely candidates are HCN, NH3, and N2. The relative abundances of these carriers ...determine the composition of planetesimals as a function of disk radius due to strong differences in their volatility. A significant sequestration of nitrogen in carriers less volatile than N2 is likely required to deliver even small amounts of nitrogen to the Earth and potentially habitable exoplanets. While HCN has been detected in small amounts in inner disks (<10 au), so far only relatively insensitive upper limits on inner disk NH3 have been obtained. We present new Gemini-TEXES high-resolution spectroscopy of the 10.75 m band of warm NH3, and use two-dimensional radiative transfer modeling to improve previous upper limits by an order of magnitude to at 1 au. These NH3 abundances are significantly lower than those typical for ices in circumstellar envelopes ( ). We also consistently retrieve the inner disk HCN gas abundances using archival Spitzer spectra, and derive upper limits on the HCN ice abundance in protostellar envelopes using archival ground-based 4.7 m spectroscopy (HCNice/H2Oice < 1.5%-9%). We identify the NH3/HCN ratio as an indicator of chemical evolution in the disk, and we use this ratio to suggest that inner disk nitrogen is efficiently converted from NH3 to N2, significantly increasing the volatility of nitrogen in planet-forming regions.
ABSTRACTAs a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers of COVID-19–infected decedents at ...autopsy. While in some cases a history of fever and/or respiratory distress (eg, cough or shortness of breath) may suggest the diagnosis, epidemiologic studies indicate that the majority of individuals infected with COVID-19 develop mild to no symptoms. Those dying with—but not of—COVID-19 may still be infectious, however. While multiple guidelines have been issued regarding autopsy protocol in cases of suspected COVID-19 deaths, there is some variability in the recommendations. Additionally, limited recommendations to date have been issued regarding scene investigative protocol, and there is a paucity of publications characterizing COVID-19 postmortem gross and histologic findings. A case of sudden unexpected death due to COVID-19 is presented as a means of illustrating common autopsy findings, as well as diagnostic and biosafety considerations. We also review and summarize the current COVID-19 literature in an effort to provide practical evidence-based biosafety guidance for medical examiner-coroner offices encountering COVID-19 at autopsy.
Abstract We present the discovery of a gravitationally lensed dust-reddened QSO at z = 2.517, identified in a survey for QSOs by infrared selection. Hubble Space Telescope imaging reveals a quadruply ...lensed system in a cusp configuration, with a maximum image separation of ∼1.″8. We find that, compared to the central image of the cusp, the neighboring brightest image is anomalous by a factor of ∼7–10, which is the largest flux anomaly measured to date in a lensed QSO. Incorporating high-resolution Very Large Array radio imaging and submillimeter imaging with the Atacama Large Millimeter/submillimeter Array, we conclude that a low-mass perturber is the most likely explanation for the anomaly. The optical through near-infrared spectrum reveals that the QSO is moderately reddened with E ( B − V ) ≃ 0.7–0.9. We see an upturn in the ultraviolet spectrum due to ∼1% of the intrinsic emission being leaked back into the line of sight, which suggests that the reddening is intrinsic and not due to the lens. The QSO may have an Eddington ratio as high as L / L Edd ≈ 0.2. Consistent with previous red QSO samples, this source exhibits outflows in its spectrum, as well as morphological properties suggestive of it being in a merger-driven transitional phase. We find a host galaxy stellar mass of log M ⋆ / M ⊙ = 11.4 , which is higher than the local M BH versus M ⋆ relation but consistent with other high-redshift QSOs. When demagnified, this QSO is at the knee of the luminosity function, allowing for the detailed study of a more typical moderate-luminosity infrared-selected QSO at high redshift.
Abstract
Background
FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer ...(BRPC) remains debated.
Methods
We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III–IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method.
Results
We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval CI = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III–IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX.
Conclusions
This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.
Toxin B (TcdB) is a major virulence factor of
, a Gram-positive pathogen that is a leading cause of hospital-acquired diarrhea. While previous studies have established that TcdB can engage multiple ...cell surface receptors
, little is known about how these interactions promote disease and where these receptors localize on colonic tissue. Here, we used immunofluorescence microscopy to visualize Nectin-3 and CSPG4 on tissue, revealing unexpected localization of both receptors on colonic epithelial cells. We show that Nectin-3, which was previously characterized as an adherens junction protein, is also localized to the brush border of colonocytes. Staining for CSPG4 revealed that it is present along epithelial cell junctions, suggesting that it is shed by fibroblasts along the crypt-surface axis. Collectively, our study provides new insights into how TcdB can gain access to the receptors Nectin-3 and CSPG4 to intoxicate colonic epithelial cells.
Background & Aims Rectal indomethacin, a nonsteroidal anti-inflammatory drug, is given to prevent pancreatitis in high-risk patients undergoing endoscopic retrograde cholangiopancreatography (ERCP), ...based on findings from clinical trials. The European Society for Gastrointestinal Endoscopy guidelines recently recommended prophylactic rectal indomethacin for all patients undergoing ERCP, including those at average risk for pancreatitis. We performed a randomized controlled trail to investigate the efficacy of this approach. Methods We performed a prospective, double-blind, placebo-controlled trial of 449 consecutive patients undergoing ERCP at Dartmouth Hitchcock Medical Center, from March 2013 through December 2014. Approximately 70% of the cohort were at average risk for PEP. Subjects were assigned randomly to groups given either a single 100-mg dose of rectal indomethacin (n = 223) or a placebo suppository (n = 226) during the procedure. The primary outcome was the development of post-ERCP pancreatitis (PEP), defined by new upper-abdominal pain, a lipase level more than 3-fold the upper limit of normal, and hospitalization after ERCP for 2 consecutive nights. Results There were no differences between the groups in baseline clinical or procedural characteristics. Sixteen patients in the indomethacin group (7.2%) and 11 in the placebo group (4.9%) developed PEP ( P = .33). Complications and the severity of PEP were similar between groups. Per a priori protocol guidelines, the study was stopped owing to futility. Conclusions In a randomized controlled study of consecutive patients undergoing ERCP, rectal indomethacin did not prevent post-ERCP pancreatitis. ClincialTrials.gov no: NCT01774604.
We present high-resolution spectroscopy of mid-infrared molecular emission from two very active T Tauri stars, AS 205 N and DR Tau. In addition to measuring high signal-to-noise line profiles of ...water, we report the first spectrally resolved mid-infrared line profiles of HCN emission from protoplanetary disks. The similar line profiles and temperatures of the HCN and water emission indicate that they arise in the same volume of the disk atmosphere, within 1-2 au of the star. The results support the earlier suggestion that the observed trend of increasing HCN/water emission with disk mass is a chemical fingerprint of planetesimal formation and core accretion in action. In addition to directly constraining the emitting radii of the molecules, the high-resolution spectra also help break degeneracies between temperature and column density in deriving molecular abundances from low-resolution mid-infrared spectra. As a result, they can improve our understanding of the extent to which inner disks are chemically active. Contrary to predictions from HCN excitation studies carried out for AS 205 N, the mid-infrared and near-infrared line profiles of HCN are remarkably similar. The discrepancy may indicate that HCN is not abundant beyond a few au or that infrared pumping of HCN does not dominate at these distances.
Abstract Observations of the ejecta from the final flash (FF) of helium shell burning in Sakurai’s Object (V4334 Sgr) are presented for 2015–2019, a period ∼20–24 yr after discovery. Adaptive optics ...images at K s trace the expanding debris. While most of the ejecta mass is in ∼200 K dust, a small fraction, ∼0.4%, of the dust mass is at ∼760 K. The 760 K continuum dominates the near-IR images. Spatial-spectral images in He i 10830 Å show an ∼16 diameter bipolar planetary nebula at position angle 21° ± 5° with the SW moving toward us and the NE moving away. Seen in integrated light, the nebula is nearly circular. Near-IR continuum images show ejecta moving radially away from a bright central point source. High-resolution mid-IR spectra reveal molecular hydrocarbon lines with an expansion velocity of 270 ± 5 km s −1 seen in absorption against the dust continuum. The hydrocarbons originate in material produced in the FF. The bipolar nebula and debris clouds are discussed in the context of a highly inclined disk model. The proper motion has been measured placing V4334 Sgr in the thick disk population. There is no evidence that a hot white dwarf Wolf–Rayet (WR) wind has emerged; no WR spectral features were detected. The possibility of a binary companion involved in the evolution is discussed.
Objective
To use quantitative magnetic resonance imaging (MRI) to test whether mediobasal hypothalamic (MBH) gliosis is associated with obesity and insulin resistance in humans.
Methods
Sixty‐seven ...participants underwent a fasting blood draw and MRI. Cases with radiologic evidence of MBH gliosis (N = 22) were identified as the upper tertile of left MBH T2 relaxation time and were compared to controls (N = 23) from the lowest tertile. In a separate postmortem study, brain slices (N = 10) through the MBH were imaged by MRI and stained for glial fibrillary acidic protein (GFAP).
Results
In all participants, longer T2 relaxation time in the left MBH was associated with higher BMI (P = 0.01). Compared with controls, cases had longer T2 relaxation times in the right MBH (P < 0.05), as well as higher BMI (P < 0.05), fasting insulin concentrations (P < 0.01), and HOMA‐IR values (P < 0.01), adjusted for sex and age. Elevations in insulin and HOMA‐IR were also independent of BMI. In the postmortem study, GFAP staining intensity was positively associated with MBH T2 relaxation time (P < 0.05), validating an MRI‐based method for the detection of MBH gliosis in humans.
Conclusions
These findings link hypothalamic gliosis to insulin resistance in humans and suggest that the link is independent of the level of adiposity.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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