Clinical and epidemiologic data in coronavirus disease (COVID-19) have accrued rapidly since the outbreak, but few address the underlying pathophysiology.
To ascertain the physiologic, hematologic, ...and imaging basis of lung injury in severe COVID-19 pneumonia.
Clinical, physiologic, and laboratory data were collated. Radiologic (computed tomography (CT) pulmonary angiography
= 39 and dual-energy CT DECT,
= 20) studies were evaluated: observers quantified CT patterns (including the extent of abnormal lung and the presence and extent of dilated peripheral vessels) and perfusion defects on DECT. Coagulation status was assessed using thromboelastography.
In 39 consecutive patients (male:female, 32:7; mean age, 53 ± 10 yr range, 29-79 yr; Black and minority ethnic,
= 25 64%), there was a significant vascular perfusion abnormality and increased physiologic dead space (dynamic compliance, 33.7 ± 14.7 ml/cm H
O; Murray lung injury score, 3.14 ± 0.53; mean ventilatory ratios, 2.6 ± 0.8) with evidence of hypercoagulability and fibrinolytic "shutdown". The mean CT extent (±SD) of normally aerated lung, ground-glass opacification, and dense parenchymal opacification were 23.5 ± 16.7%, 36.3 ± 24.7%, and 42.7 ± 27.1%, respectively. Dilated peripheral vessels were present in 21/33 (63.6%) patients with at least two assessable lobes (including 10/21 47.6% with no evidence of acute pulmonary emboli). Perfusion defects on DECT (assessable in 18/20 90%) were present in all patients (wedge-shaped,
= 3; mottled,
= 9; mixed pattern,
= 6).
Physiologic, hematologic, and imaging data show not only the presence of a hypercoagulable phenotype in severe COVID-19 pneumonia but also markedly impaired pulmonary perfusion likely caused by pulmonary angiopathy and thrombosis.
Muscle impairment is a common condition in older people and a powerful risk factor for disability and mortality. The aim of this study was to apply the European Working Group on Sarcopenia in Older ...People criteria to estimate the prevalence and investigate the clinical correlates of sarcopenia, in a sample of Italian community-dwelling older people.
Cross-sectional analysis of 730 participants (74% aged 65 years and older) enrolled in the InCHIANTI study. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People criteria using bioimpedance analysis for muscle mass assessment. Logistic regression analysis was used to identify the factors independently associated with sarcopenia.
Sarcopenia defined by the European Working Group on Sarcopenia in Older People criteria increased steeply with age (p < .001), with 31.6% of women and 17.4% of men aged 80 years or older being affected by this condition. Higher education (odds ratio: 0.85; 95% CI: 0.74-0.98), lower insulin-like growth factor I (lowest vs highest tertile, odds ratio: 3.89; 95% CI: 1.03-14.1), and low bioavailable testosterone (odds ratio: 2.67; 95% CI: 1.31-5.44) were independently associated with the likelihood of being sarcopenic. Nutritional intake, physical activity, and level of comorbidity were not associated with sarcopenia.
Sarcopenia identified by the European Working Group on Sarcopenia in Older People criteria is a relatively common condition in Italian octogenarians, and its prevalence increases with aging. Correlates of sarcopenia identified in this study might suggest new approaches for prevention and treatment of sarcopenia.
We have studied similar to 2100 early-type galaxies in the SDSS DR3 which have been detected by the GALEX Medium Imaging Survey (MIS), in the redshift range 0 < z < 0.11. Combining GALEX UV ...photometry with corollary optical data from the SDSS, we find that, at a 95% confidence level, at least similar to 30% of galaxies in this sample have UV to optical colors consistent with some recent star formation within the last Gyr. In particular, galaxies with an NUV - r color less than 5.5 are very likely to have experienced such recent star formation, taking into account the possibility of a contribution to NUV flux from the UV upturn phenomenon. We find quantitative agreement between the observations and the predictions of a semianalytical Lambda CDM hierarchical merger model and deduce that early-type galaxies in the redshift range 0 < z < 0.11 have similar to 1%-3% of their stellar mass in stars less than 1 Gyr old. The average age of this recently formed population is similar to 300-500 Myr. We also find that "monolithically" evolving galaxies, where recent star formation can be driven solely by recycled gas from stellar mass loss, cannot exhibit the blue colors (NUV - r < 5.5) seen in a significant fraction ( similar to 30%) of our observed sample.
Histone deacetylase (HDAC) inhibitors have been extensively investigated as therapeutic agents in cancer. However, the biological role of class IIa HDACs (HDAC4, 5, 7 and 9) in cancer cells, ...including multiple myeloma (MM), remains unclear. Recent studies show HDAC4 interacts with activating transcription factor 4 (ATF4) and inhibits activation of endoplasmic reticulum (ER) stress-associated proapoptotic transcription factor C/EBP homologous protein (CHOP). In this study, we hypothesized that HDAC4 knockdown and/or inhibition could enhance apoptosis in MM cells under ER stress condition by upregulating ATF4, followed by CHOP. HDAC4 knockdown showed modest cell growth inhibition; however, it markedly enhanced cytotoxicity induced by either tunicamycin or carfilzomib (CFZ), associated with upregulating ATF4 and CHOP. For pharmacological inhibition of HDAC4, we employed a novel and selective class IIa HDAC inhibitor TMP269, alone and in combination with CFZ. As with HDAC4 knockdown, TMP269 significantly enhanced cytotoxicity induced by CFZ in MM cell lines, upregulating ATF4 and CHOP and inducing apoptosis. Conversely, enhanced cytotoxicity was abrogated by ATF4 knockdown, confirming that ATF4 has a pivotal role mediating cytotoxicity in this setting. These results provide the rationale for novel treatment strategies combining class IIa HDAC inhibitors with ER stressors, including proteasome inhibitors, to improve patient outcome in MM.
Human semen is heterogeneous in quality, not only between males but also within a single ejaculate. Differences in quality are evident, both when examining the classical parameters of sperm number, ...motility and morphology and in the integrity of the sperm nucleus. The aim of this study was to determine the efficiency of the PureSperm®, Percoll® and swim-up preparation techniques to eliminate spermatozoa with nuclear anomalies. Semen samples were collected, washed and one part of the semen spread on a slide, the remainder was prepared using the swim-up, PureSperm® or Percoll® techniques. Spermatozoa from different fractions were fixed on slides and assessed. Sperm samples (n) from different men were stained using the chromomycin A3 (CMA3) fluorochrome, which indirectly demonstrates a decreased presence of protamine (n = 31 for swim-up; n = 45 for PureSperm®; n = 39 for Percoll®). Spermatozoa prepared using PureSperm® (n = 35) and Percoll® (n = 37) were also examined for the presence of endogenous DNA nicks. Good quality spermatozoa should not possess DNA nicks and not stain (i.e. fluoresce) with CMA3. When prepared using the swim-up technique the spermatozoa recovered showed no significant improvement with the CMA3 staining. When spermatozoa were prepared using the PureSperm® and Percoll® techniques, a significant (P < 0.001) decrease in both CMA3 positivity and DNA strand breakage was observed. These results indicate that both the PureSperm® and Percoll® techniques can enrich the sperm population by separating out those with nicked DNA and with poorly condensed chromatin.
Summary
The clinical characteristics associated with hidradenitis suppurativa (HS) severity are poorly understood. In this study, 124 patients with HS from 6 Italian dermatology centres participated ...in this study. Disease severity was assessed using the Hidradenitis Suppurativa Physician's Global Assessment score (HS‐PGA) and Hurley score. The impact of clinical characteristics on disease severity was assessed by logistic regression. Clinical characteristics were similar between men (n = 53) and women (n = 71). Disease severity was also similar; 75% of the patients had Hurley stage II or III disease, and > 60% had moderate, severe or very severe HS as judged by HS‐PGA. Lesions were more frequent in the gluteal region in men (32.3% in men vs. 8.7% in women, P < 0.001) and more frequent on the breast in women (16.3% in women vs. 4.6% in men, P = 0.02). Obesity was associated with increased disease severity as measured by HS‐PGA (OR: 3.28, 95% CI 1.55–6.95, P < 0.01) and Hurley classification (OR: 3.22, 95% CI 1.34–7.31, P < 0.01). Although severity of HS is similar between the sexes, the localization of lesions is different.
We use GALEX near-UV (NUV) photometry of a sample of early-type galaxies selected in the SDSS (Sloan Digital Sky Survey) to study the UV color-magnitude relation (CMR). NUV - r color is an excellent ...tracer of even small amounts ( similar to 1% mass fraction) of recent ( unk1 Gyr) star formation, and so the NUV - r CMR allows us to study the effect of environment on the recent star formation history. We analyze a volume-limited sample of 839 visually inspected early-type galaxies in the redshift range 0.05 < z < 0.10 brighter than M sub(r) of -21.5 with any possible emission-line or radio-selected active galactic nuclei (AGNs) removed to avoid contamination. We find that contamination by AGN candidates and late-type interlopers highly bias any study of recent star formation in early-type galaxies and that, after removing those, our lower limit to the fraction of massive early-type galaxies showing signs of recent star formation is roughly 30% plus or minus 3%. This suggests that residual star formation is common even among the present day early-type galaxy population. We find that the fraction of UV-bright early-type galaxies is 25% higher in low-density environments. However, the density effect is clear only in the lowest density bin. The blue galaxy fraction for the subsample of the brightest early-type galaxies, however, shows a very strong density dependence, in the sense that the blue galaxy fraction is lower in a higher density region.
Purpose
Physical examinations and annual mammography (minimal follow-up) are as effective as laboratory/imaging tests (intensive follow-up) in detecting breast cancer (BC) recurrence. This statement ...is now challenged by the availability of new diagnostic tools for asymptomatic cases. Herein, we analyzed current practices and circulating tumor DNA (ctDNA) in monitoring high-risk BC patients treated with curative intent in a comprehensive cancer center.
Patients and methods
Forty-two consecutive triple negative BC patients undergoing neoadjuvant therapy and surgery were prospectively enrolled. Data from plasma samples and surveillance procedures were analyzed to report the diagnostic pattern of relapsed cases, i.e., by symptoms, follow-up procedures and ctDNA.
Results
Besides minimal follow-up, 97% and 79% of patients had at least 1 non-recommended imaging and laboratory tests for surveillance purposes. During a median follow-up of 5.1(IQR, 4.1–5.9) years, 13 events occurred (1 contralateral BC, 1 loco-regional recurrence, 10 metastases, and 1 death). Five recurrent cases were diagnosed by intensive follow-up, 5 by symptoms, and 2 incidentally. ctDNA antedated disseminated disease in all evaluable cases excepted two with bone-only and single liver metastases. The mean time from ctDNA detection to suspicious findings at follow-up imaging was 3.81(SD, 2.68), and to definitive recurrence diagnosis 8(SD, 2.98) months. ctDNA was undetectable in the absence of disease and in two suspected cases not subsequently confirmed.
Conclusions
Some relapses are still symptomatic despite the extensive use of intensive follow-up. ctDNA is a specific test, sensitive enough to detect recurrence before other methods, suitable for clarifying equivocal imaging, and exploitable for salvage therapy in asymptomatic BC survivors.
We compare the dust attenuation properties of two samples of galaxies purely selected in the Galaxy Evolution Explorer (GALEX) near-ultraviolet band (NUV; 1750-2750 Å, λmean=2310 Å) and in the ...far-infrared (FIR) at 60 μm. These samples are built using the GALEX and IRAS sky surveys over ~600 deg2. The NUV-selected sample contains 95 galaxies detected down to NUV=16 mag (AB system). Eighty-three galaxies in this sample are spiral or irregular, and only two of them are not detected at 60 μm. The FIR-selected sample is built from the IRAS PSCz survey, which is complete down to 0.6 Jy. Among the 163 sources, we select 118 star-forming galaxies that are well measured by IRAS; all but one are detected in NUV, and 14 galaxies are not detected in the far-ultraviolet band (FUV; 1350-1750 Å, λmean=1530 Å). The dust-to-ultraviolet (NUV and FUV) flux ratio is calibrated to estimate the dust attenuation at both wavelengths. The median value of the attenuation in NUV is found to be ~1 mag for the NUV-selected sample, versus ~2 mag for the FIR-selected one. Within both samples, the dust attenuation is found to correlate with the luminosity of the galaxies. Almost all the NUV-selected galaxies and two-thirds of the FIR-selected sample exhibit a lower dust attenuation than expected from the tight relation found previously for starburst galaxies between dust attenuation and the slope of the ultraviolet continuum. The situation is reversed for the remaining third of the FIR-selected galaxies: their extinction is higher than that deduced from their FUV-NUV color and the relation for starbursts.
Mid-infrared observations of the Andromeda galaxy, M31, obtained with the Infrared Array Camera on board the Spitzer Space Telescope are presented. The image mosaics cover areas of approximately 3.7 ...x 1.6 and include the satellite galaxies M32 and NGC 205. The appearance of M31 varies dramatically in the different mid-infrared bands, from the smooth bulge and disk of the old stellar population seen at 3.6 km to the well-known "10 kpc ring" dominating the 8 km image. The similarity of the 3.6 km and optical isophotes and the nearly constant optical-mid-infrared color over the inner 400" confirm that there is no significant extinction at optical wavelengths in M31's bulge. The nuclear colors indicate the presence of dust but not an infrared-bright active galactic nucleus. The integrated 8 km nonstellar luminosity implies a star formation rate of 0.4 M sub( )yr super(-1) consistent with other indicators that show M31 to be a quiescent galaxy.
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