The COVID-19 pandemic is likely to represent an ongoing global health issue given the potential for new variants, vaccine escape and the low likelihood of eliminating all reservoirs of the disease. ...Whilst diagnostic testing has progressed at a fast pace, the metabolic drivers of outcomes-and whether markers can be found in different biofluids-are not well understood. Recent research has shown that serum metabolomics has potential for prognosis of disease progression. In a hospital setting, collection of saliva samples is more convenient for both staff and patients, and therefore offers an alternative sampling matrix to serum. Saliva samples were collected from hospitalised patients with clinical suspicion of COVID-19, alongside clinical metadata. COVID-19 diagnosis was confirmed using RT-PCR testing, and COVID-19 severity was classified using clinical descriptors (respiratory rate, peripheral oxygen saturation score and C-reactive protein levels). Metabolites were extracted and analysed using high resolution liquid chromatography-mass spectrometry, and the resulting peak area matrix was analysed using multivariate techniques. Positive percent agreement of 1.00 between a partial least squares-discriminant analysis metabolomics model employing a panel of 6 features (5 of which were amino acids, one that could be identified by formula only) and the clinical diagnosis of COVID-19 severity was achieved. The negative percent agreement with the clinical severity diagnosis was also 1.00, leading to an area under receiver operating characteristics curve of 1.00 for the panel of features identified. In this exploratory work, we found that saliva metabolomics and in particular amino acids can be capable of separating high severity COVID-19 patients from low severity COVID-19 patients. This expands the atlas of COVID-19 metabolic dysregulation and could in future offer the basis of a quick and non-invasive means of sampling patients, intended to supplement existing clinical tests, with the goal of offering timely treatment to patients with potentially poor outcomes.
•A consumer-oriented type of innovative service provider (knowledge-intensive consumer services - KICS) is identified, defined and distinguished from KIBS.•A key characteristic of KICS is a double ...differentiation trajectory in which both hard and soft powers to innovate are combined.•Research on KICS should focus on the actual dynamic capabilities from which innovations emerge without neglecting potential contributions to science and technology.•New and alternative indicators are important in capturing innovation in KIBS.•Evidence is taken from the dentistry and oral surgery area, which has received little attention in the field of innovation studies.
This paper explores a case of knowledge-intensive consumer services (KICS). Services have become less neglected in the economics of technical change and innovation studies in general; nevertheless, the advance of this agenda has been uneven. A significant emphasis has been on knowledge-intensive business services (KIBS). Despite their direct impact on social needs and individual desires, innovation in consumer-oriented services continues to be relatively under-theorized and under-researched. This paper brings into focus the sources and patterns of innovation in those innovative services that target human satisfaction and well-being as a final goal. We show evidence from a little-explored health industry, oral care. We address Malo Clinic, a company specialized in the most complex patient situations and a rare instance of an internationalized firm in the health services business. On the basis of a 20-year thread of corporate history, we find that a wide array of qualitative (interviews, newspaper coverage, marketing material) and quantitative evidence (papers, patents, trademarks) illuminates some of the features that may characterize a particular class of dynamic activities tending to consumers’ needs, expectations and quality of life. We argue that these key characteristics may be on course to become more general as the learning economy spreads to fully embrace the realm of the service sphere. One conclusion is that both the technological and non-technological capabilities underpinning more types of innovation are increasingly becoming coupled in consumer-relevant services.
The radical ring-opening polymerization (RROP) of thionolactones provides access to thioester backbone-functional copolymers but has, to date, only been demonstrated on acrylic copolymers. Herein, ...the thionolactone dibenzoc,eoxepane-5-thione (DOT) was subjected to azobisisobutyronitrile (AIBN)-initiated free-radical homopolymerization, which produced a thioester-functional homopolymer with a glass-transition temperature of 95 °C and the ability to degrade exclusively into predetermined small molecules. However, the homopolymerization was impractically slow and precluded the introduction of functionality. Conversely, the reversible addition–fragmentation chain-transfer (RAFT)-mediated copolymerization of DOT with N-methylmaleimide (MeMI), N-phenylmaleimide (PhMI), and N-2,3,4,5,6-pentafluorophenylmaleimide (PFPMI) rapidly produced well-defined copolymers with the tendency to form alternating sequences increasing in the order MeMI ≪ PhMI < PFPMI, with estimated reactivity ratios of r DOT = 0.198 and r PFPMI = 0.0078 for the latter system. Interestingly, defects in the alternating structure were more likely caused by (degradable) DOT–DOT sequences rather than (nondegradable) MI–MI sequences, which was confirmed through the paper spray mass spectrometric analysis of the products from aminolytic degradation. Upon the aminolysis of backbone thioesters, maleimide repeating units were ring-opened, forming bisamide structures. Conversely, copolymer degradation through a thiolate did not result in imide substitution but nucleophilic para-fluoro substitution on PFPMI comonomer units, indicating the ability of DOT–MI copolymers to degrade under different conditions and to form differently functional products. The RROP of thionolactones has distinct advantages over the RROP of cyclic ketene acetals and is anticipated to find use in the development of well-defined degradable polymer materials.
Wide QRS arrhythmia: what is the diagnosis? Oliveira, Cátia Costa; Rocha, Sérgia; Magalhães, Sónia
Emergency medicine journal : EMJ,
02/2022, Volume:
39, Issue:
2
Journal Article
Peer reviewed
Ventricular tachycardia Pre-excited atrial fibrillation Antidromic atrioventricular re-entrant tachycardia Aberrant conduction during atrial fibrillation Answer Case resolution The ECG shows a wide ...QRS complex tachycardia with irregular RR intervals, delta waves and no P waves, findings suggestive of Wolff-Parkinson-White syndrome with pre-excited atrial fibrillation (AF) (figure 1). Pre-excited AF should be suspected in the presence of a wide and irregular QRS complex tachycardia, especially with an unusually high frequency (compared with non- excited AF); an initial slurred upstroke or downstroke of the QRS (epicardial activation); QRS complexes exhibiting varying morphology (varying degrees of fusion due to activation over both the accessory pathway (AP) and the atrioventricular (AV) node); or positive precordial concordance (entirely positive R wave in all precordial leads with no R/S complexes).1 All these findings can be seen in this case (figure 2). Management of asymptomatic arrhythmias: a European heart rhythm association (EHRA) consensus document, endorsed by the heart failure association (HFA), heart rhythm Society (HRS), Asia Pacific heart rhythm Society (APHRS), cardiac arrhythmia Society of southern Africa (CASSA), and Latin America heart rhythm Society (LAHRS).
Although outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions (PCI) have improved, women show higher mortality.
To ...assess gender differences in presentation, management and in-hospital mortality, at 30-days, 6-months and 1-year after STEMI.
We retrospectively collected data from 809 consecutive patients treated with primary PCI and compared the females versus males at the local intervention cardiology database. The level of significance used was p<0.05.
Women were older than man (69,1±14,6 vs. 58,5±12,7 years; p<.001) with higher prevalence of age over 75 years (36.7% vs. 11.7%; p<.001), diabetes (30,6% vs. 18,5%; p=.001), hypertension (60.5% vs. 45.9%; p=.001), chronic kidney disease (3.4% vs. 0.6%; p=.010) and acute ischemic stroke (6.8% vs. 3.0%; p=.021). At presentation, women had more atypical symptoms, less chest pain (p=.014) and were more frequently in cardiogenic shock (p=.011)). Women had longer time until reperfusion (p=.001) and were less likely to receive optimal medical therapy (p<0.05). In-hospital mortality (p=.001), at 30-days (p<.001), 6-months (p<.001) and 1-year (16.4% vs. p<.001) was higher in women. The multivariate analysis identified age over 75 years (HR=4.25; 95% CI1.67-10.77;p=.002), Killip class II (HR=8.80; 95% CI2.72-28.41;p<.001), III (HR=5.88; 95% CI 0.99-34.80; p=.051) and IV (HR=9.60; 95% CI1.86-48.59;p=.007), Acute Kidney Injury (HR=2.47; 95% CI1.00-6.13;p=.051) and days of hospitalization (HR=1.04; 95% CI1.01-1.08;p=.030) but not female gender (HR=0.83; 95% CI0.33-2.10;p=.690) as independent prognostic factors of mortality.
Compared to men, women with STEMI undergoing primary PCI have higher mortality rates. Women admitted for STEMI have a worse risk profile, are treated with a higher reperfusion time related with system delays and are less likely to receive the recommended therapy. Female gender was not an independent prognostic factor for mortality in the studied population.
Protein secretion in eukaryotes and prokaryotes involves a universally conserved protein translocation channel formed by the Sec61 complex. Unrelated small-molecule natural products and synthetic ...compounds inhibit Sec61 with differential effects for different substrates or for Sec61 from different organisms, making this a promising target for therapeutic intervention. To understand the mode of inhibition and provide insight into the molecular mechanism of this dynamic translocon, we determined the structure of mammalian Sec61 inhibited by the Mycobacterium ulcerans exotoxin mycolactone via electron cryo-microscopy. Unexpectedly, the conformation of inhibited Sec61 is optimal for substrate engagement, with mycolactone wedging open the cytosolic side of the lateral gate. The inability of mycolactone-inhibited Sec61 to effectively transport substrate proteins implies that signal peptides and transmembrane domains pass through the site occupied by mycolactone. This provides a foundation for understanding the molecular mechanism of Sec61 inhibitors and reveals novel features of translocon function and dynamics.
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•The inhibited Sec translocon adopts a conformation optimal for substrate engagement•The inhibitor mycolactone wedges open the lateral gate of Sec61α•Mycolactone blocks the path taken by the signal peptide during engagement•Resistance mutations are likely to operate by modulating translocon dynamics
Gérard et al. determine the structure of the mammalian Sec translocon in an inhibited state. Mycolactone holds the translocon in a conformation optimal for substrate engagement, wedging open the cytosolic side of the lateral gate, while also blocking the path taken by the signal peptide during engagement.
The ultra-stable Y (H-USY) zeolite is used as catalyst for the conversion of plastic feedstocks into high added value products through catalytic cracking technologies. However, the energy ...requirements associated with these processes are still high. On the other hand, induction heating by magnetic nanoparticles has been exploited for different applications such as cancer treatment by magnetic hyperthermia, improving of water electrolysis and many other heterogeneous catalytic processes. In this work, the heating efficiency of γ-Fe2O3 nanoparticle impregnated zeolites is investigated in order to determine the potential application of this system in catalytic reactions promoted by acid catalyst centers under inductive heating. The γ-Fe2O3 nanoparticle impregnated zeolite has been investigated by X-ray diffraction, electron microscopy, ammonia temperature program desorption (NH3-TPD), H2 absorption, thermogravimetry and dc and ac-magnetometry. It is observed that the diffusion of the magnetic nanoparticles in the pores of the zeolite is possible due to a combined micro and mesoporous structure and, even when fixed in a solid matrix, they are capable of releasing heat as efficiently as in a colloidal suspension. This opens up the possibility of exploring the application at higher temperatures.
Patients with ST-elevation myocardial infarction (STEMI) requiring inter-hospital transfer for primary percutaneous coronary intervention (PCI) often have delays in reperfusion. The door in-door out ...(DIDO) time is recommended to be less than 30 min.
To assess the DIDO time of hospitals that transfer patients with STEMI to a PCI center and to assess its impact on total ischemia time and clinical outcomes in patients with STEMI.
We performed a retrospective study of 523 patients with STEMI transferred to a PCI center for primary PCI between January 1, 2013 and June 30, 2017.
Median DIDO time was 82 min (interquartile range, 61–132 min). Only seven patients (1.3%) were transferred in ≤30 min. Patients with DIDO times over 60 min had significantly longer system delays (207.3 min vs. 112.7 min; p<0.001) and total ischemia time (344.2 min vs. 222 min; p<0.001) than patients transferred in ≤60 min. Observed in-hospital mortality was significantly higher among patients with DIDO times >60 min vs. ≤60 min (5.1% vs. 0%; p=0.006; adjusted odds ratio for in-hospital mortality, 1.27 95% CI 1.062–1.432). By the end of follow-up, patients belonging to the >60 min group had a higher mortality (p=0.016), and survival time was significantly shorter (p=0.011).
A DIDO time ≤30 min was observed in only a small proportion of patients transferred for primary PCI. DIDO times of ≤60 min were associated with shorter delays in reperfusion, lower in-hospital mortality and longer survival times.
Está recomendado que os doentes com enfarte agudo do miocárdio com supra de ST (EAMcSST) que necessitam de transferência inter-hospitalar para a intervenção coronária percutânea primária (ICPP) tenham um tempo de door in-door out (DIDO) ≤30 minutos.
Avaliar o tempo DIDO dos hospitais que transferem pacientes com EAMcSST para ICP e o seu impacto no tempo total de isquemia e outcomes clínicos.
Estudo retrospetivo com 523 doentes com EAMcSST transferidos para a ICPP, entre 1 de janeiro de 2013 e 30 de junho de 2017.
A mediana do tempo DIDO foi de 82 minutos (intervalo interquartílico IQ, 61-132 minutos). Apenas 7 pacientes (1,3%) foram transferidos em ≤30 minutos. Os pacientes com um tempo DIDO >60 minutos apresentavam atrasos de sistema (207,3 min versus 112,7 min; p<0,001) e tempos totais de isquemia (344,2 min versus 222 min; p<0,001) significativamente superiores quando comparados com os doentes que eram transferidos em ≤60 minutos. A mortalidade intra-hospitalar foi significativamente superior nos pacientes com tempo DIDO >60 minutos (5,1% versus 0%; p=0,006; odds ratio ajustada para a mortalidade intra-hospitalar, 1,27 95% IC, 1,062-1,432). Até à data de follow-up, os doentes pertencentes ao grupo “>60 min” apresentavam uma maior proporção de eventos de morte, p=0,016 e o tempo de sobrevivência era significativamente inferior, p=0,011.
O tempo DIDO ≤30 minutos foi observado numa pequena proporção de doentes. DIDO ≤60 minutos associaram-se a menores atrasos na reperfusão, a menor mortalidade intra-hospitalar e a maiores tempos de sobrevivência.
The current paper implementates a simple fully non-linear Kirchhoff-lovel shell penalty based finite element. The 6 nodes and 21 DoF triangular element developed in this work has a quadratic ...displacement field associated to it and the C1 continuity required by Kirchhoff-Love Hyphotesis is approximated by an internal penalty. The biggest novelty in this article is the simultaneous use of penalty and a Rodrigues incremental Rotation parameter (scalar DOF) between neighboring elements further explained in the text. The nonlinear finite element model developed in this article is compared to analytical results, commercial finite element code and another FEM model developed in bibliography. Simulations have demonstrated consistency when comparing results to other models and it is deemed that reliable mesh generation together with a powerfull triangular finite element is a good option for trustworthy thin shell simulations.
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