Risk of acute pulmonary embolism in COVID-19 pneumonia compared to community-acquired pneumonia: a retrospective case-control study.

AIM: To compare the incidence of pulmonary embolism (PE) in COVID-19 pneumonia and non-COVID-19-related community-acquired pneumonia (CAP) in hospitalised patients. MATERIALS AND METHODS: A retrospective case-control study was conducted. This included patients hospitalised with pneumonia and investigated for suspected PE with computed tomography pulmonary angiogram (CTPA). Cases were defined as patients with COVID-19 pneumonia from 1 March 2020 to 17 May 2020; controls were patients with CAP from 5 July 2019 to 31 January 2020. The primary outcome was to determine the risk of developing PE in both groups. Multivariable logistic regression was used to calculate the adjusted odds ratio for PE. RESULTS: One hundred and forty-four patients were included; 72 cases (47% male; mean age 59 (±15) years), and 72 controls (56% male; mean age 58 (±20) years). PE was diagnosed in 23.6% of the cases versus 6.9% of the controls. The adjusted odds ratio for PE in hospitalised patients with COVID-19 pneumonia compared with those with CAP was 3.23 (95% confidence interval [CI] 1.04-10.04, p=0.04). CONCLUSION: The odds of developing PE in hospitalised patients with COVID-19 pneumonia are three-times higher than in those with CAP. The results provide a quantitative assessment of the risk of PE in COVID-19 pneumonia, a condition new to healthcare, compared to other forms of pneumonia with a well-established scientific basis.

Warfarin dosing after bariatric surgery: a retrospective study of 10 patients previously stable on chronic warfarin therapy.

Many changes associated with bariatric surgery have the potential to affect warfarin dosing; yet current literature includes little data describing this phenomenon. Investigating this relationship may allow for determination of post-bariatric surgery warfarin dosing using stable pre-operative dosing levels. A retrospective chart review was completed for 10 patients stabilized on chronic warfarin therapy who underwent bariatric surgery. Data collection consisted of the following: warfarin requirement in mg/week, time in target range (TTR), creatinine, liver function, diarrhoea, medication changes, diet, and signs of bleeding and/or thrombosis. Three study patients underwent laparoscopic adjustable gastric banding procedures and seven patients underwent Roux-en-Y gastric bypass. The average (standard deviation) weekly warfarin dose required in the immediate post-operative interval was 64% (25%) of baseline dosing, corresponding to a TTR of 48%. At 6 months, patients required 85% (19%) of baseline weekly dosing, with TTR of 53.4%. At 1 year, dosing was 90% (16%) of baseline with TTR of 63.5%. Patients underwent medication changes as well as transient bouts of diarrhoea. Two patients suffered unspecified haemorrhages of the gastrointestinal tract (international normalized ratio [INR] = 2.3 and 9.8). This patient set demonstrated an initial drop in warfarin requirement, followed by escalating dosing trends that became more predictable as patients were farther out from procedure.

Evaluation of a breast support conveyor to improve poultry welfare on the shackle line.

A breast support conveyor has the potential to improve bird welfare by avoiding the need to invert and suspend broilers by their legs as they move from the point of shackling to entry into the electric waterbath. To evaluate its effect on welfare under commercial conditions, a breast support conveyor was installed under the conventional shackle line of a small poultry processing plant. A structured assessment of the behaviour of the birds indicated a significant decrease in struggling and wing flapping at the point of shackling, on the straight conveyor and at entry into the waterbath. This resulted in a lower prevalence of red wing tips and bruising in the first wing joint. The shackle line and conveyor in this installation, however, passed around a 90° corner, which appeared to cause more disturbance to the birds on the conveyor than to comparable birds suspended from shackles in the traditional manner. The results indicate that a breast support conveyor has the potential to improve bird welfare on straight shackle lines and that, because struggling activity and duration following shackling are reduced, the time between shackling and stunning could also be reduced using this method, further improving bird welfare. Breast support conveyors should not be used when the shackle lines have sharp bends.

Effect of environment on Pekin duck behaviour and its correlation with body condition on commercial farms in the UK.

1. Forty-six flocks of commercially-reared Pekin ducks were studied to determine the effects of housing system and environment on the behaviour of farmed ducks and its correlation with physical condition. Houses differed predominantly in their ventilation, drinking, feeding and brooding systems, and were indicative of systems currently in use in the UK. 2. At 41 d of age ducks spent 15% of the time feeding, 67% drinking, 42% rooting and 155% dry preening. They spent large amounts of time relatively inactive, 435%, or performing comfort behaviours, 17%. On average 46% of their time was spent walking and only 18% wet preening. 3. A greater proportion of the maximum number of ducks able to use the drinker at any one time used the trough; nipple use was least and Plasson use intermediate. The proportion of ducks wet preening was not affected by drinker type but increased with increasing drinker space (mm/bird). 4. Duck behaviour was little affected by commercial production system and was influenced more by environment, age and physical condition. Activity at an older age incorporated more of the behaviours associated with thermal comfort (panting) and maintenance of plumage condition (dry and wet preening). These behaviours increased with increasing temperature, relative humidity and atmospheric ammonia. Poor walking ability was correlated to increased frequency of panting, reduced activity at the drinker, and longer resting bouts.

Environment and management factors affecting Pekin duck production and welfare on commercial farms in the UK.

1. Forty-six flocks of commercially-reared Pekin ducks were studied in 23 houses differing in their ventilation and brooding systems, and water and feed resources, in order to identify factors affecting duck welfare in commercial practice. 2. A wide range of environmental variables were measured, together with the physical and plumage condition of the ducks at two ages, whilst companies supplied mortality and growth rate data. 3. At 23 d, more than 98% of ducks had clean eyes, nostrils and feathers and an upright posture, and 86% had no gait abnormalities. By 41 d, body condition had deteriorated slightly with 84% of ducks having clean eyes, 67% clean feathers and 79% no gait abnormalities. 4. Gait worsened with increasing temperature and litter moisture, and atmospheric ammonia concentrations. The incidence of foot pad lesions was 10% (moderate) and 3% (severe) and was positively correlated with increasing humidity and ammonia. 5. Average mortality rates were 52% for ducks reared to 335 kg at 48 d with average growth rates of 603 to 813 g/d. High temperatures correlated with high mortality and reduced growth rate; growth rate was not related to poor gait. 6. Controlling the ducks' environment, particularly temperature, humidity, litter moisture and ammonia is crucial to duck welfare. Effective ventilation systems, high quality straw and access to some form of open water were considered important for duck welfare.

Resting discharge patterns of macular primary afferents in otoconia-deficient mice.

Vestibular primary afferents in the normal mammal are spontaneously active. The consensus hypothesis states that such discharge patterns are independent of stimulation and depend instead on excitation by vestibular hair cells due to background release of synaptic neurotransmitter. In the case of otoconial sensory receptors, it is difficult to test the independence of resting discharge from natural tonic stimulation by gravity. We examined this question by studying discharge patterns of single vestibular primary afferent neurons in the absence of gravity stimulation using two mutant strains of mice that lack otoconia (OTO-; head tilt, het-Nox3, and tilted, tlt-Otop1). Our findings demonstrated that macular primary afferent neurons exhibit robust resting discharge activity in OTO- mice. Spike interval coefficient of variation (CV = SD/mean spike interval) values reflected both regular and irregular discharge patterns in OTO- mice, and the range of values for rate-normalized CV was similar to mice and other mammals with intact otoconia although there were proportionately fewer irregular fibers. Mean discharge rates were slightly higher in otoconia-deficient strains even after accounting for proportionately fewer irregular fibers [OTO- = 75.4 +/- 31.1(113) vs OTO+ = 68.1 +/- 28.5(143) in sp/s]. These results confirm the hypothesis that resting activity in macular primary afferents occurs in the absence of ambient stimulation. The robust discharge rates are interesting in that they may reflect the presence of a functionally 'up-regulated' tonic excitatory process in the absence of natural sensory stimulation.

The VIZIER project: preparedness against pathogenic RNA viruses.

Life-threatening RNA viruses emerge regularly, and often in an unpredictable manner. Yet, the very few drugs available against known RNA viruses have sometimes required decades of research for development. Can we generate preparedness for outbreaks of the, as yet, unknown viruses? The VIZIER (VIral enZymes InvolvEd in Replication) (http://www.vizier-europe.org/) project has been set-up to develop the scientific foundations for countering this challenge to society. VIZIER studies the most conserved viral enzymes (that of the replication machinery, or replicases) that constitute attractive targets for drug-design. The aim of VIZIER is to determine as many replicase crystal structures as possible from a carefully selected list of viruses in order to comprehensively cover the diversity of the RNA virus universe, and generate critical knowledge that could be efficiently utilized to jump-start research on any emerging RNA virus. VIZIER is a multidisciplinary project involving (i) bioinformatics to define functional domains, (ii) viral genomics to increase the number of characterized viral genomes and prepare defined targets, (iii) proteomics to express, purify, and characterize targets, (iv) structural biology to solve their crystal structures, and (v) pre-lead discovery to propose active scaffolds of antiviral molecules.

Effect of seed size on seedling growth response to elevated CO2 in Picea abies and Picea rubens.

Several previous studies have observed that species and individuals with large seeds respond more positively to elevated CO (2) than those with small seeds. We explored the reasons for this pattern by examining the relationship between seed size and CO (2) response in Picea abies and P. rubens using growth analysis. The large seeded species (P. abies) responded more positively to elevated CO (2) than the small seeded species (P. rubens). At the intraspecific level, P. abies individuals from large seeds responded more positively to elevated CO (2) than individuals from small seeds, however, there was no significant intraspecific variation in CO (2) response in P. rubens. The greater CO (2) response of plants from large seeds was not simply the result of a larger starting capital compounded at the same rate as in plants from small seeds. Elevated CO (2) increased relative growth rate to a greater extent in individuals from large seeds. This effect appears to be related to differences in time of establishment, source to sink ratio and nutrient availability with seed size. These results are significant not only in understanding the potential effect of rising atmospheric CO (2) concentrations on plant populations, but also in understanding the factors affecting plant success at current atmospheric CO (2) levels due to the elevation of CO (2) within the litter layer that occurs at many germination sites.

Leaf-level acclimation to gap creation in mature Acer saccharum trees.

Leaf-level morphological and physiological responses of mature, winter-deciduous, shade-tolerant Acer saccharum Marsh. trees to gap formation caused by selection harvest were studied experimentally over a 2-year period. We found no evidence for either physiological stress or positive acclimation following gap creation during the 1-2-week post-harvest period. Rather, lower-canopy leaves showed gradual increases in area-based maximum photosynthetic rates (Amax-area), stomatal conductance (gs), and leaf nitrogen concentration (Narea) over the entire 2-year study. These acclimation responses were directly related to changes in leaf mass per unit area (LMA) in the subsequent two leaf flushes. No change in Amax-area, gs, Narea, or photosynthetic nitrogen-use efficiency was observed that could not be accounted for by changes in LMA. The gradual acclimation responses in the lower canopy may account, in whole or in part, for the approximately 2-year lag in post-harvest growth response observed in Acer saccharum.

Abnormalities in skilled reaching movements are improved by peripheral anesthetization of the less-affected forelimb after sensorimotor cortical infarcts in rats.

Unilateral damage to sensorimotor cortical (SMC) regions can profoundly impair skilled reaching function in the contralesional forelimb. Such damage also results in impairments and compensatory changes in the less-affected/ipsilesional forelimb, but these effects remain poorly understood. Furthermore, anesthetization of the ipsilesional hand in humans with cerebral infarcts has been reported to produce transient functional improvements in the paretic hand [Floel A, Nagorsen U, Werhahn KJ, Ravindran S, Birbaumer N, Knecht S, et al. Influence of somatosensory input on motor function in patients with chronic stroke. Ann Neurol 2004;56:206-12; Voller B, Floel A, Werhahn KJ, Ravindran S, Wu CW, Cohen LG. Contralateral hand anesthesia transiently improves poststroke sensory deficits. Ann Neurol 2006;59:385-8]. One aim of this study was to sensitively assay the bilateral effects of unilateral ischemic SMC damage on performance of a unimanual skilled reaching task (the single pellet retrieval task) that rats had acquired pre-operatively with each forelimb. The second aim was to determine whether partially recovered contralesional reaching function is influenced by anesthetization of the ipsilesional forelimb. Unilateral SMC lesions were found to result in transient ipsilesional impairments in reaching success and significant ipsilesional abnormalities in reaching movements compared with sham-operates. There were major contralesional reaching impairments which improved during a 4 week training period, but movements remained significantly abnormal. Anesthetization of the ipsilesional forelimb with lidocaine at this time attenuated the contralesional movement abnormalities. These findings indicate that unilateral ischemic SMC lesions impair skilled reaching behavior in both forelimbs. Furthermore, after partial recovery in the contralesional forelimb, additional improvements can be induced by transient anesthetization of the ipsilesional forelimb. This is consistent with the effects of unilateral anesthetization in humans which have been attributed to the modulation of competitive interhemispheric interactions. The present findings suggest that such interactions are also likely to influence skilled reaching function in rats.

Application of the use of high-throughput technologies to the determination of protein structures of bacterial and viral pathogens.

The Structural Proteomics In Europe (SPINE) programme is aimed at the development and implementation of high-throughput technologies for the efficient structure determination of proteins of biomedical importance, such as those of bacterial and viral pathogens linked to human health. Despite the challenging nature of some of these targets, 175 novel pathogen protein structures (approximately 220 including complexes) have been determined to date. Here the impact of several technologies on the structural determination of proteins from human pathogens is illustrated with selected examples, including the parallel expression of multiple constructs, the use of standardized refolding protocols and optimized crystallization screens.

Environmental and management factors affecting the welfare of chickens on commercial farms in the United Kingdom and Denmark stocked at five densities.

Data from a large commercial-scale experiment in which 10 major broiler producer companies stocked whole houses of birds at 30, 34, 38, 42, and 46 kg/m2 were analyzed to identify 1) temperature and humidity profiles achieved throughout the growth cycle, 2) management practices and equipment that contributed to observed variation in environmental conditions, and 3) the extent to which environmental variables affected bird welfare. The study involved a total of 2.7 million birds in 114 houses on commercial farms with measurement of a wide range of environmental and bird variables. Much of the variation in broiler health and welfare was associated with the percentage of time a company could maintain house temperature and RH within limits recommended by the breeder company. RH in the first week of life was particularly important to later health, suggesting that better control of humidity might lead to improved welfare. Key management factors affecting bird welfare were those relating to good ventilation and air control such as the type of ventilation, type of drinker, numbers of stockmen, and litter type. Controlling the environment, particularly temperature, humidity, and air and litter quality, is crucial to broiler chicken welfare. This does not mean that stocking density is unimportant, but lowering stocking density on its own, without regard to the environment the birds experience, is not sufficient. Genuine improvements in bird welfare will come from setting standards that combine stocking density, safeguards on the environment, and the genetic makeup of the birds.

Training the "less-affected" forelimb after unilateral cortical infarcts interferes with functional recovery of the impaired forelimb in rats.

PURPOSE: Unilateral lesions of the sensorimotor cortex (SMC) in adult rats cause major behavioral changes in the ipsilesional, "less-affected" forelimb. An increase in function and reliance on this forelimb can aid compensation for contralesional impairments, but may also promote disuse and reduced functionality of the impaired forelimb. We hypothesized that training focused on the ipsilesional forelimb following a unilateral SMC lesion would reduce the efficacy of later motor rehabilitative training of the impaired forelimb. METHODS: Rats with ischemic SMC lesions were trained on a skilled reaching task with the ipsilesional forelimb (PriorT) or received control procedures (Cont) for 10 days. Both groups were then trained with the impaired forelimb on the same reaching task for 10 days. RESULTS: In comparison with Cont, PriorT rats had little improvement on the reaching task with the impaired forelimb and had a more enduring disuse of the impaired forelimb for postural support behaviors. Lesion sizes were similar between groups. CONCLUSIONS: Behavioral experience with the less-affected forelimb early after unilateral SMC lesions has the potential to increase disuse and dysfunction of the impaired forelimb, consistent with a training-induced exacerbation of learned non-use. These findings are suggestive of competitive processes in experience-dependent neural restructuring after brain damage.

Evidence for macular gravity receptor modulation of hypothalamic, limbic and autonomic nuclei.

Mice lacking normal vestibular gravity reception show altered homeostatic, circadian and autonomic responses to hypergravity (+G) exposure. Using c-Fos as a marker of neuronal activation, the current study identifies CNS nuclei that may be critical for initiating and integrating such responses to changes in vestibular signaling. This experiment utilized the mutant C57BL/6JEi-het mouse (het), which lacks macular otoconia and thus gravity receptor function. Following 2 h of 2G (2x Earth's gravity) exposure (via centrifugation) the neuronal responses of the het mice were compared with wildtype mice similarly exposed to 2G, as well as het and wildtype 1G controls. Wildtype mice exposed to 2G demonstrated robust c-Fos expression in multiple autonomic, hypothalamic and limbic nuclei, including: the lateral septum, bed nucleus of the stria terminalis, amygdala, paraventricular hypothalamus, dorsomedial hypothalamus, arcuate, suprachiasmatic hypothalamus, intergeniculate leaflet, dorsal raphe, parabrachial and locus coeruleus. The het mice exposed to 2G demonstrated little to null c-Fos expression in these nuclei with a few exceptions and, in general, a similar pattern of c-Fos to 1G controls. Data from this study further support the existence of a complex and extensive influence of the neurovestibular system on homeostatic, circadian and possibly autonomic regulatory systems.

Behavioral and neuroplastic effects of focal endothelin-1 induced sensorimotor cortex lesions.

Previous studies have established the usefulness of endothelin-1 (ET-1) for the production of focal cerebral ischemia. The present study assessed the behavioral effects of focal ET-1-induced lesions of the sensorimotor cortex (SMC) in adult rats as well as cellular and structural changes in the contralateral homotopic motor cortex at early (2 days) and later (14 days) post-lesion time points. ET-1 lesions resulted in somatosensory and postural-motor impairments in the contralateral (to the lesion) forelimb as assessed on a battery of sensitive measures of sensorimotor function. The lesions also resulted in the development of a hyper-reliance on the ipsilateral forelimb for postural-support behaviors. In comparison to sham-operated rats, in layer V of the motor cortex opposite the lesions, there were time- and laminar-dependent increases in the surface density of dendritic processes immunoreactive for microtubule-associated protein 2, in the optical density of N-methyl-D-asparate receptor (NMDA) subunit 1 immunoreactivity, and in the numerical density of cells immunolabeled for Fos, the protein product of the immediate early gene c-fos. These findings corroborate and extend previous findings of the effects of electrolytic lesions of the SMC. It is likely that compensatory forelimb behavioral changes and transcallosal degeneration play important roles in these changes in the cortex opposite the lesion, similar to previously reported effects of electrolytic SMC lesions.

Addition of rosiglitazone to metformin is most effective in obese, insulin-resistant patients with type 2 diabetes.

AIM: These analyses were undertaken to evaluate the efficacy of the insulin sensitizer rosiglitazone (RSG) when added to the therapy of obese type 2 diabetes mellitus patients (T2DM) taking near-maximal doses (2.5 g/day) of metformin (MET). In obese, insulin-resistant patients with T2DM who are inadequately controlled on MET, the addition of an agent that reduces insulin resistance may be a more rational and innovative approach than the addition of an insulin secretagogue. METHODS: Data were pooled from two double-blind studies of RSG added to 2.5 g/day MET, involving a total of 550 T2DM patients. Patients were categorized as non-overweight, overweight and obese according to their baseline BMI using WHO criteria (<25 kgm(-2), 25-30 kgm(-2), >30 kgm(-2) respectively). RESULTS: RSG improved glycaemia (HbA1c) and fasting plasma glucose (FPG) to a clinically significant extent in all three subgroups but the effect was most pronounced in the obese patients. Improvements in HOMA estimates of insulin resistance and beta-cell function were also greatest in the obese patients (4 mg: -16% and +19%; 8 mg: -37% and + 33% respectively), as were reductions in fasting insulin. The profile of adverse events was not demonstrably different in obese patients from the non-obese. CONCLUSIONS: In obese type 2 diabetic patients inadequately controlled on MET alone, addition of rosiglitazone improves glycaemic control, insulin sensitivity and beta-cell function to a clinically important extent.

Primordial rhythmic bursting in embryonic cochlear ganglion cells.

This study examined the nature of spontaneous discharge patterns in cochlear ganglion cells in embryonic day 13 (E13) to early E17 chicken embryos (stages 39-43). Neural recordings were made with glass micropipettes. No sound-driven activity was seen for the youngest embryos (maximum intensity 107 dB sound pressure level). Ganglion cells were labeled with biotinylated dextran amine in four embryos. In two animals, primary afferents projected to hair cells in the middle region along the length of the basilar papilla in which, in one cell, the terminals occupied a neural transverse position and, in the other, a more abneural location. Statoacoustic ganglion cells showing no spontaneous activity were seen for the first time in the chicken. The proportion of "silent" cells was largest at the youngest stages (stage 39, 67%). In active cells, mean spontaneous discharge rates [9.4 +/- 10.4 spikes (Sp)/sec; n = 44] were lower than rates for older embryos (19 +/- 17 Sp/sec) (Jones and Jones, 2000). Embryos at stages 39-41 evidenced even lower rates (4.2 +/- 5.0 Sp/sec). The most salient feature of spontaneous activity for stages 39-43 was a bursting discharge pattern in >75% of active neurons (33 of 44). Moreover, in 55% of these cells, there was a clear, slow, rhythmic bursting pattern. The proportion of cells showing rhythmic bursting was greatest at the youngest stages (39-42) and decreased to <30% at stage 43. Rate of bursting ranged from 1 to 54 bursts per minute. The presence of rhythmic bursting in cochlear ganglion cells at E13-E17 provides an explanation for the existence of such patterns in central auditory relays. The bursting patterns may serve as a patterning signal for central synaptic refinements in the auditory system during development.

Computational identification of noncoding RNAs in E. coli by comparative genomics.

Some genes produce noncoding transcripts that function directly as structural, regulatory, or even catalytic RNAs [1, 2]. Unlike protein-coding genes, which can be detected as open reading frames with distinctive statistical biases, noncoding RNA (ncRNA) gene sequences have no obvious inherent statistical biases [3]. Thus, genome sequence analyses reveal novel protein-coding genes, but any novel ncRNA genes remain invisible. Here, we describe a computational comparative genomic screen for ncRNA genes. The key idea is to distinguish conserved RNA secondary structures from a background of other conserved sequences using probabilistic models of expected mutational patterns in pairwise sequence alignments. We report the first whole-genome screen for ncRNA genes done with this method, in which we applied it to the "intergenic" spacers of Escherichia coli using comparative sequence data from four related bacteria. Starting from >23,000 conserved interspecies pairwise alignments, the screen predicted 275 candidate structural RNA loci. A sample of 49 candidate loci was assayed experimentally. At least 11 loci expressed small, apparently noncoding RNA transcripts of unknown function. Our computational approach may be used to discover structural ncRNA genes in any genome for which appropriate comparative genome sequence data are available.

Bouveret's syndrome presenting as upper gastrointestinal hemorrhage without hematemesis.

A 74-year-old woman with a recent diagnosis of peptic ulcer disease diagnosed by endoscopy after presentation with an episode of upper gastrointestinal bleeding returned 6 1/2 weeks later with a 5-day history of nausea and vomiting without associated symptoms. An ultrasound was nondiagnostic except for a large gallstone and a poorly visualized gallbladder. Repeat endoscopy revealed a hard mass that was presumed to have formed secondarily to an ulcer-induced stricture, and a 6-cm filling defect just proximal to the duodenal bulb was seen on a preoperative upper gastrointestinal series. At laparotomy the mass was actually a large gallstone and two smaller stones, which had eroded into and become impacted in the duodenal bulb creating a gastric outlet obstruction. The stones were extracted via a duodenotomy, and the remaining portion of the gallbladder was removed with repair of the cholecystoduodenal fistula. The patient was discharged home after an uncomplicated postoperative course. Gastric outlet obstruction by a duodenal gallstone is a condition known as Bouveret's syndrome, which is a rare complication of gallstone disease. Upper gastrointestinal hemorrhage is an especially rare form of presentation.