Right Ventricular Dysfunction in Ventilated Patients with COVID-19 (COVID-RV)

PurposeCOVID-19 is associated with cardiovascular complications, with right ventricular dysfunction (RVD) commonly reported. The combination of acute respiratory distress syndrome (ARDS), injurious invasive ventilation, micro/macro thrombi and the potential for direct myocardial injury create conditions where RVD is likely to occur. No study has prospectively explored the prevalence of RVD, and its association with mortality, in a cohort requiring mechanical ventilation. MethodsProspective, multi-centre, trans-thoracic echocardiographic, cohort study of ventilated patients with COVID-19 in Scottish intensive care units. RVD was defined as the presence of severe RV dilatation and interventricular septal flattening. To explore role of myocardial injury, high sensitivity troponin and N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured in all patients. ResultsOne hundred and twenty-one patients were recruited to COVID-RV, 118 underwent imaging and it was possible to determine the primary outcome in 112. RVD was present in seven (6.2% [95%CI; 2.5%, 12.5%]) patients. Thirty-day mortality was 85.7% in those with RVD, compared to 44.8% in those without (p=0.051). Patients with RVD were more likely to have; pulmonary thromboembolism (p<0.001), higher plateau pressure (p=0.048), lower dynamic compliance (p=0.031), higher NT-proBNP (p<0.006) and more frequent abnormal troponin (p=0.048). Abnormal NT-proBNP (OR 4.77 [1.22, 21.32], p=0.03) and abnormal Troponin (16.54 [4.98, 67.12], p<0.001) independently predicted 30-day mortality. ConclusionCOVID-RV demonstrates a prevalence of RVD in ventilated patients with COVID-19 of 6.2% and is associated with a mortality of 85.7%. Association is observed between RVD and each of the aetiological domains of; ARDS, ventilation, micro/macro thrombi and myocardial injury.

Pharmacogenetics of osteoporosis-related bone fractures: moving towards the harmonization and validation of polymorphism diagnostic tools.

Osteoporosis is one of the most common skeletal chronic conditions in developed countries, hip fracture being one of its major healthcare outcomes. There is considerable variation in the implementation of current pharmacological treatment and prevention, despite consistent recommendations and guidelines. Many studies have reported conflicting findings of genetic associations with bone density and turnover that might predict fracture risk. Moreover, it is not clear whether genetic differences exist in relation to the morbidity and efficiency of the pharmacotherapy treatments. Clinical response, including beneficial and adverse events associated with osteoporosis treatments, is highly variable among individuals. In this context, the present article intends to summarize putative candidate genes and genome-wide association studies that have been related with BMD and fracture risk, and to draw the attention to the need for pharmacogenetic methodology that could be applicable in clinical translational research after an adequate validation process. This article mainly compiles analysis of important polymorphisms in osteoporosis documented previously, and it describes the simple molecular biology tools for routine genotype acquisition. Validation of methods for the easy, fast and accessible identification of SNPs is necessary for evolving pharmacogenetic diagnostic tools in order to contribute to the discovery of clinically relevant genetic variation with an impact on osteoporosis and its personalized treatment.

Developing cryopreservation for Picea sitchensis (sitka spruce) somatic embryos: a comparison of vitrification protocols.

Two vitrification-based cryopreservation protocols, encapsulation/dehydration and PVS2 were applied to Stage 2 (globular) and Stage 4 (torpedo) somatic embryos (SE) from Picea sitchensis. Two recovery responses: partially differentiated embryogenic suspensor masses (ESM) and dedifferentiated non-embryogenic masses (NEM) were observed following exposure to LN. All genotypes tested, proliferated NEM, approximately 10 to 100% of the total SE cryopreserved. A General Linear Model applied to NEM recovery data demonstrated several different factors (developmental state and genotype, treatment, culture age) interacted at a significant level (P less than 0.05) to influence proliferation. One genotype was capable of proliferating ESM after cryopreservation using encapsulation-dehydration, this response was achieved for Stage 4 embryos derived from the youngest ESM tissue.

Monolithic Active Pixel Sensors (MAPS) in a Quadruple Well Technology for Nearly 100% Fill Factor and Full CMOS Pixels.

In this paper we present a novel, quadruple well process developed in a modern 0.18 mm CMOS technology called INMAPS. On top of the standard process, we have added a deep P implant that can be used to form a deep P-well and provide screening of N-wells from the P-doped epitaxial layer. This prevents the collection of radiation-induced charge by unrelated N-wells, typically ones where PMOS transistors are integrated. The design of a sensor specifically tailored to a particle physics experiment is presented, where each 50 mm pixel has over 150 PMOS and NMOS transistors. The sensor has been fabricated in the INMAPS process and first experimental evidence of the effectiveness of this process on charge collection is presented, showing a significant improvement in efficiency.

Cryopreservation of Picea sitchensis (sitka spruce) embryogenic suspensor masses.

A cryopreservation method comprising sorbitol pre-growth treatment, DMSO cryoprotection and two-step controlled rate cooling has been optimized for differentiated embryogenic suspensor masses (ESM) of Picea sitchensis. The protocol was applied to clonal cultures from five different half-sibling families each represented by five different genotypes and their responses to cryopreservation assessed over 3 years. Nineteen of the 25 clonal lines tested survived LN and were capable of regrowth and producing stage 2-4 somatic embryos. Following the second subculture cycle of esm after they had been retrieved from cryogenic storage, post-cryopreservation regrowth was comparable with that of controls. A general linear model, multifactorial main effects plot revealed no significant differences between genotypes (p > 0.05) in response to cryopreservation, whereas significant differences between families (p < 0.05) were detected.

Studies on poly(trimethylene terephthalate) filaments containing silver.

Two methods were used to incorporate silver ions into poly(trimethylene terephthalate) (PTT) fibers. The first technique involved the direct addition of silver (I) sulfadiazine into PTT polymer prior to extrusion. The second method involved the use of silver-exchanged zeolites. Although no optimization with silver-exchanged zeolites was conducted, this study clearly showed that PTT fibers containing sufficient amounts of silver ions are effective in reducing pathological-microorganisms such as Escherichia coli. Incorporation of silver-exchanged zeolites into PTT imparted a silver color to the fibers which may be attributed to the partial reduction of silver ions during spinning at 256 degrees C. Because of the decomposition of silver (I) sulfadiazine, the spinnability of PTT fiber sample was not satisfactory and, therefore, this compound cannot be used as a carrier of silver ions in PTT. The thermal, tensile and antimicrobial properties of the spun filaments are reported in this paper.

Effect of chronic cocaine administration and cocaine withdrawal on coronary flow rate and heart rate responses to epinephrine and cocaine in isolated perfused rat hearts.

The acute dose-dependent effects of epinephrine and cocaine on heart rate and coronary flow rate (CFR) were examined in isolated, perfused (Langendorff) rat hearts from animals: i) pretreated with daily cocaine injections (20 mg/kg/day) for 8 weeks; ii) after 2-day withdrawal from 8-week cocaine pretreatment; iii) vehicle-treated controls. Chronic cocaine (CC) hearts were significantly less sensitive to the chronotropic effects of epinephrine than control (C) or withdrawal (CW) hearts. CW hearts exhibited significantly higher heart rates in response to epinephrine than C and CC hearts. Epinephrine alone (2.5 x 10(-7) M) decreased CFR 11% (C), 9%(CC), 14%(CW) from respective baseline levels. Cocaine alone had no significant effect on CFR in C hearts but produced slight dose-dependent decrements in CFR in CC and particularly CW hearts at higher doses. Cocaine plus epinephrine markedly decreased CFR in all groups, particularly in CW hearts. The results indicate that chronic daily cocaine administration produces a functional tolerance of the heart to the chronotropic actions of epinephrine but a 2-day withdrawal from chronic cocaine results in a rebound supersensitivity to adrenergic stimulation and cocaine's sympathomimetic effects. In addition, cocaine produces only minor decrements in coronary flow in the rat heart, while cocaine acts synergisticallly with epinephrine to produce a marked decrease in CFR.