Multislice computed tomography (MSCT) has recently evolved as a modality for noninvasive coronary imaging.
To assess the accuracy and robustness of MSCT vs the criterion standard of invasive coronary ...angiography for detection of obstructive coronary artery disease.
Prospective, single-center study conducted in a referral center setting in Germany and enrolling 103 consecutive patients (mean age, 61.5 SD, 9.7 years) from November 2003-August 2004 who were undergoing both invasive coronary angiography and MSCT using a scanner with 16 detector rows.
Blinded results for both modalities compared using the patient as the primary unit of analysis, with supplementary segment- and vessel-based analyses.
One thousand three hundred eighty-four segments (> or =1.5 mm diameter) were identified by invasive coronary angiography; nondiagnostic image quality of MSCT was identified for only 88 (6.4%) of these segments, mainly due to faster heart rates. Compared with invasive coronary angiography for detection of significant lesions (>50% stenosis), segment-based sensitivity, specificity, and positive and negative predictive values of MSCT were 95%, 98%, 87%, and 99%, respectively. Quantitative comparison of MSCT and invasive coronary angiography showed good correlation (r = 0.87, P<.001), with MSCT systematically measuring greater-percentage stenoses (bias, +12%). In the patient-based analysis, the area under the receiver operating characteristic curve was 0.97 (95% confidence interval, 0.90-1.00), indicating high discriminative power to identify patients who might be candidates for revascularization (>50% left main artery stenosis and/or >70% stenosis in any other epicardial vessel). Threshold optimization allowed either detection of these patients with 100% sensitivity at a reasonable false-positive rate (specificity, 76.5%; MSCT stenosis, >66%) or optimization of both the sensitivity and specificity (>90%; MSCT stenosis, >76%).
Multislice computed tomography provides high accuracy for noninvasive detection of suspected obstructive coronary artery disease. This promising technology has potential to complement diagnostic invasive coronary angiography in routine clinical care.
Although lung disease is the primary clinical outcome in COVID-19 patients, how SARS-CoV-2 induces lung pathology remains elusive. Here we describe a high-throughput platform to generate ...self-organizing and commensurate human lung buds derived from hESCs cultured on micropatterned substrates. Lung buds resemble human fetal lungs and display proximodistal patterning of alveolar and airway tissue directed by KGF. These lung buds are susceptible to infection by SARS-CoV-2 and endemic coronaviruses and can be used to track cell type-specific cytopathic effects in hundreds of lung buds in parallel. Transcriptomic comparisons of infected lung buds and postmortem tissue of COVID-19 patients identified an induction of BMP signaling pathway. BMP activity renders lung cells more susceptible to SARS-CoV-2 infection and its pharmacological inhibition impairs infection by this virus. These data highlight the rapid and scalable access to disease-relevant tissue using lung buds that recapitulate key features of human lung morphogenesis and viral infection biology.
•Derivation of self-organizing and commensurate lung buds on microchips from hESCs•Lung buds display in vivo-like proximo-distal patterning of lung tissue•Parallelized quantitative analysis of SARS-CoV-2 viral life cycle in lung buds•Identification of BMP signaling as a key mediator of SARS-CoV-2 infection via ACE2
Brivanlou and colleagues describe a high-throughput platform to generate self-organizing human lung buds from hESCs on microchips. Lung buds display in vivo-like proximo-distal patterning of lung tissue, and are amenable to high-throughput quantitative analysis of SARS-CoV-2 cell type-specific infection, transmission, and cytopathology. Transcriptomic comparisons with COVID-19 postmortem tissues identified the BMP signaling pathway as a key regulator of SARS-CoV-2 infection.
In 2014, the International Endohernia Society (IEHS) published the first international “Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias.” Guidelines reflect the ...currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature.
Methods
For the development of the original guidelines, all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based Medicine. For the present update, all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne), the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included.
Results
Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques—minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite insufficient evidence with respect to these new techniques, it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields.
Conclusion
Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initial guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.
Milk yield per cow has continuously increased in many countries over the last few decades. In addition to potential economic advantages, this is often considered an important strategy to decrease ...greenhouse gas (GHG) emissions per kg of milk produced. However, it should be considered that milk and beef production systems are closely interlinked, as fattening of surplus calves from dairy farming and culled dairy cows play an important role in beef production in many countries. The main objective of this study was to quantify the effect of increasing milk yield per cow on GHG emissions and on other side effects. Two scenarios were modelled: constant milk production at the farm level and decreasing beef production (as co-product; Scenario 1); and both milk and beef production kept constant by compensating the decline in beef production with beef from suckler cow production (Scenario 2). Model calculations considered two types of production unit (PU): dairy cow PU and suckler cow PU. A dairy cow PU comprises not only milk output from the dairy cow, but also beef output from culled cows and the fattening system for surplus calves. The modelled dairy cow PU differed in milk yield per cow per year (6000, 8000 and 10 000 kg) and breed. Scenario 1 resulted in lower GHG emissions with increasing milk yield per cow. However, when milk and beef outputs were kept constant (Scenario 2), GHG emissions remained approximately constant with increasing milk yield from 6000 to 8000 kg/cow per year, whereas further increases in milk yield (10 000 kg milk/cow per year) resulted in slightly higher (8%) total GHG emissions. Within Scenario 2, two different allocation methods to handle co-products (surplus calves and beef from culled cows) from dairy cow production were evaluated. Results showed that using the ‘economic allocation method’, GHG emissions per kg milk decreased with increasing milk yield per cow per year, from 1.06 kg CO₂ equivalents (CO₂ₑq) to 0.89 kg CO₂ₑq for the 6000 and 10 000 kg yielding dairy cow, respectively. However, emissions per kg of beef increased from 10.75 kg CO₂ₑq to 16.24 kg CO₂ₑq due to the inclusion of suckler cows. This study shows that the environmental impact (GHG emissions) of increasing milk yield per cow in dairy farming differs, depending upon the considered system boundaries, handling and value of co-products and the assumed ratio of milk to beef demand to be satisfied.
Objective Venous diseases are among the most frequent diseases in the general population of industrialized countries. The aim of this article is to investigate the population-based prevalence of ...pathologic reflux in superficial and deep leg veins, taking into account factors as gender, age, and clinical classification of venous disease. Methods In a population-based cross-sectional study, 3072 subjects aged 18 to 79 years (1350 male, 1722 female, response 59%) were enrolled from October 2000 through November 2001. A standardized interview was conducted to document phlebological history and clinical examinations including duplex sonography of selected superficial and deep leg veins. Pathological reflux was defined as being >500 ms. All participants where classified according to the CEAP classification. Results Using the highest clinical stage per participant, 9.6% where classified C0, 59.0% C1, 14.3% C2, 13.5% C3, 2.9% C4, and 0.7% C5-C6. A pathological reflux (>500 ms) was found in 35.3% (95% confidence interval CI 33.6-37.1) of subjects with 21.0% (95% CI 19.5-22.5) showing reflux in at least one superficial vein and 20.0% (95% CI 18.6-21.5) showing reflux in at least one deep vein. We observed significantly higher reflux prevalence for the superficial veins in women while for the deep veins reflux prevalence were significantly higher in men. Prevalence of reflux in the superficial veins markedly increases with age. In the deep venous system, no clear changes in reflux prevalence with age can be observed. For superficial veins, reflux prevalence is markedly higher with higher C-stages. For the deep veins, the proportion of refluxes is relatively constant in stages C0-C3 with a distinct increase of prevalence from stage C4 onward. Conclusion Our results show a high prevalence of reflux both for the superficial and the deep venous system. Reflux prevalence is associated with gender, age, and the clinical stage as measured by the CEAP classification. Further longitudinal studies are needed to clarify the relevance of pathological reflux in subjects with otherwise healthy veins.
Diet-induced increase in body weight is a growing health concern worldwide. Often accompanied by a low-grade metabolic inflammation that changes systemic functions, diet-induced alterations may ...contribute to neurodegenerative disorder progression as well. This study aims to non-invasively investigate diet-induced metabolic and inflammatory effects in the brain of an APPPS1 mouse model of Alzheimer's disease.
FFDG,
FFTHA, and
FGE-180 were used for in vivo PET imaging in wild-type and APPPS1 mice. Ex vivo flow cytometry and histology in brains complemented the in vivo findings.
H- magnetic resonance spectroscopy in the liver, plasma metabolomics and flow cytometry of the white adipose tissue were used to confirm metaflammatory condition in the periphery. We found disrupted glucose and fatty acid metabolism after Western diet consumption, with only small regional changes in glial-dependent neuroinflammation in the brains of APPPS1 mice. Further ex vivo investigations revealed cytotoxic T cell involvement in the brains of Western diet-fed mice and a disrupted plasma metabolome.
H-magentic resonance spectroscopy and immunological results revealed diet-dependent inflammatory-like misbalance in livers and fatty tissue. Our multimodal imaging study highlights the role of the brain-liver-fat axis and the adaptive immune system in the disruption of brain homeostasis in amyloid models of Alzheimer's disease.
During haze periods in the North China Plain, extremely high NO concentrations have been observed, commonly exceeding 1 ppbv, preventing the classical gas-phase H2O2 formation through HO2 ...recombination. Surprisingly, H2O2 mixing ratios of about 1 ppbv were observed repeatedly in winter 2017. Combined field observations and chamber experiments reveal a photochemical in-particle formation of H2O2, driven by transition metal ions (TMIs) and humic-like substances (HULIS). In chamber experiments, steady-state H2O2 mixing ratios of 116 ± 83 pptv were observed upon the irradiation of TMI- and HULIS-containing particles. Correspondingly, H2O2 formation rates of about 0.2 ppbv h–1 during the initial irradiation periods are consistent with the H2O2 rates observed in the field. A novel chemical mechanism was developed explaining the in-particle H2O2 formation through a sequence of elementary photochemical reactions involving HULIS and TMIs. Dedicated box model studies of measurement periods with relative humidity >50% and PM2.5 ≥ 75 μg m–3 agree with the observed H2O2 concentrations and time courses. The modeling results suggest about 90% of the particulate sulfate to be produced from the SO2 reaction with OH and HSO3 – oxidation by H2O2. Overall, under high pollution, the H2O2-caused sulfate formation rate is above 250 ng m–3 h–1, contributing to the sulfate formation by more than 70%.
The journey from plasma membrane to nuclear pore is a critical step in the lifecycle of DNA viruses, many of which must successfully deposit their genomes into the nucleus for replication. Viral ...capsids navigate this vast distance through the coordinated hijacking of a number of cellular host factors, many of which remain unknown. We performed a gene-trap screen in haploid cells to identify host factors for adenovirus (AdV), a DNA virus that can cause severe respiratory illness in immune-compromised individuals. This work identified Mindbomb 1 (MIB1), an E3 ubiquitin ligase involved in neurodevelopment, as critical for AdV infectivity. In the absence of MIB1, we observed that viral capsids successfully traffic to the proximity of the nucleus but ultimately fail to deposit their genomes within. The capacity of MIB1 to promote AdV infection was dependent on its ubiquitination activity, suggesting that MIB1 may mediate proteasomal degradation of one or more negative regulators of AdV infection. Employing complementary proteomic approaches to characterize proteins proximal to MIB1 upon AdV infection and differentially ubiquitinated in the presence or absence of MIB1, we observed an intersection between MIB1 and ribonucleoproteins (RNPs) largely unexplored in mammalian cells. This work uncovers yet another way that viruses utilize host cell machinery for their own replication, highlighting a potential target for therapeutic interventions that counter AdV infection.
To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on ...Lung Cancer was held on 11–12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.
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