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Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19.
Introduction: Epidemiologic and modeling studies suggest that between 45 and 70% of individuals with chronic hepatitis C virus (HCV) infection in Canada remain undiagnosed. The Canadian Association for the Study of the Liver (CASL) recommends one-time screening of baby boomers (1945-1975). Screening programs in the US have shown a very high prevalence of previously undiagnosed HCV among patients seen in the emergency department (ED). We sought to assess the feasibility of implementing a targeted birth-cohort HCV screening program in a Canadian ED setting. Methods: Patients born from 1945 to 1975 presenting to the ED of a downtown Toronto hospital were offered HCV testing. Patients with life-threatening conditions, unable to provide verbal consent in English or intoxication were excluded. Blood samples were collected by finger prick on Dried Blood Spot (DBS) collection cards and tested for anti-HCV antibody with reflex to HCV RNA. Patients with positive HCV RNA were referred to a liver specialist. Results: During a 27-month period (July 2017 - Sept 2019), 8363 patients in the birth cohort presented to the ED during daytime hours. 80% (6714) met eligibility criteria, and 48.4% (3247) were offered testing. Screening was performed by non-medical staff (mean 8/day, median spots on DBS 4). 345 (10.6%) had been previously tested, and 639 (19.7%) declined. 2136 (65.8%) patients underwent testing: median age 58.4 years (40-82), 1117 male (52.3%). Of these, 45 patients (2.1%; 95% CI 1.5%-2.7%) were anti-HCV positive: 32 (76.2%) were HCV RNA positive, 10 (23.8%) negative and 3 not done due to inadequate DBS sample. 26 patients (81.3%) were linked to care and 3 (9.4%) lost to follow-up. HCV prevalence in the ED was significantly higher than the general Canadian population (2.1% vs 0.7%; p < 0.0001) but much lower than reported rates in American EDs (2.1% vs 10.3%; p < 0.0001). Conclusion: Acceptance of HCV screening in the ED birth cohort was high and easily performed using DBS to ensure the majority of positive samples were tested for HCV RNA. Challenges included implementation that limited number of people tested, and linkage to care for HCV positive patients. HCV prevalence among this ED birth cohort was higher than the general population but lower than seen in the ED in the US. This may in part be due to exclusion of individuals with more severe medical issues, refusal by higher risk subgroups, or population and healthcare system differences between countries.
Aim of this contribution is to describe the intervention used in the study “Effectiveness and Cost-Effectiveness of Needs-Oriented Discharge Planning and Monitoring for High Utilisers of Psychiatric Services” (NODPAM). This intervention applies principles of needs-led care and focusses on the inpatient-outpatient transition. The NODPAM intervention manual includes a range of predefined standardised options based on number and type of needs.
For the intervention group, a trained intervention worker provides a coherent package of needs-oriented discharge planning and monitoring focussing on the care process. He or she emphasises continuity of the care process vis-à-vis both patient and clinician (and carers if possible) via providing two manualised intervention sessions): (a) A discharge planning session takes place just before discharge with the patient and responsible clinician at the inpatient service; (b) A monitoring session takes place three months after discharge with the patient and outpatient clinician (office-based or public outpatient mental health service-based). A written treatment plan is signed by and forwarded to all participants after each session.
Acceptance of the intervention by patients and clinicians has been high so far. Further results on duration, participant characteristics, and participants' appraisal of the NODPAM intervention will be presented.
These first results indicate that the NODPAM intervention is feasible in inpatient mental health services in Germany. Discussion will focus on its applicability in other service systems.
Diagnosis of schizophrenia spectrum disorders (SSD) may be difficult in clinical practice, particularly during the first episodes of early-onset psychosis (FE-EOP).
To develop a Support Vector Machine (SVM) algorithm as a predictive tool for diagnostic outcome in patients with FE-EOP, based on clinical and biomedical data at the emergence of the illness.
Two-year, prospective longitudinal study, where 81 patients (9-17 years of age) with a FE-EOP and stable diagnosis at follow-up and 41 age and sex-matched healthy controls (HC) were included. Structured diagnostic interviews, clinical and cognitive scales, a MRI scan and biochemical tests were conducted at baseline. Three SVM classification algorithms were developed (SSD vs HC group, non-SSD vs HC group, and SSD vs non-SSD group). Jackknifing was used to validate the algorithms and to calculate performance estimates. Enhanced-Recursive Feature Elimination was performed in order to gain information about the predictive weight for diagnosis of each variable.
The SSD-versus-non-SSD classifier achieved an overall accuracy of 83.1%, sensitivity of 86.6% and specificity of 77.8%. The variables during a FE-EOP with higher predictive value for a diagnosis of SSD were clinical variables such as negative symptoms preceding or during the psychotic onset, poor insight and duration of illness until first psychiatric contact. Biochemical, neuroimaging, and cognitive variables at baseline did not provide any additional predictive value.
SVM may serve as a predictive tool for early diagnosis of SSD during a FE-EOP. The most discriminative variables during a FE-EOP for a future diagnosis of SSD are clinical variables.
Because plant phenotypes can change in response to attacks by herbivores in highly variable ways, the distribution of herbivores depends on the occurrence of other herbivore species on the same plant. We carried out a field study to evaluate the co-occurrence of three coconut pests, the mites Aceria guerreronis (Acari: Eriophyidae), Steneotarsonemus concavuscutum (Acari: Tarsonemidae) and the moth Atheloca bondari (Lepidoptera: Pyralidae). The eriophyid mite Ac. guerreronis is the most important coconut pest around the world, whereas S. concavuscutum and At. bondari are economically important only in some areas along the Brazilian coast. A previous study suggested that the necrosis caused by Ac. guerreronis facilitates the infestation of At. bondari larvae. Because all three species infest the area under the perianths on coconuts and S. concavuscutum also causes necrosis that could facilitate At. bondari, we evaluated the co-occurrence of all three species. We found that the occurrence of At. bondari was positively associated with Ac. guerreronis, but negatively associated with S. concavuscutum. In addition, the two mite species showed negative co-occurrence. Atheloca bondari was found on nuts of all ages, but more on nuts that had fallen than on those on the trees, suggesting that nuts infested by At. bondari tend to fall more frequently. We discuss the status of At. bondari as a pest and discuss experiments to test the causes of these co-occurrence patterns.
Psychotic disorders are associated with metabolic abnormalities including alterations in glucose and lipid metabolism. A major challenge in the treatment of psychosis is to identify patients with vulnerable metabolic profiles who may be at risk of developing cardiometabolic co-morbidities. It is established that both central and peripheral metabolic organs use lipids to control energy balance and regulate peripheral insulin sensitivity. The endocannabinoid system, implicated in the regulation of glucose and lipid metabolism, has been shown to be dysregulated in psychosis. It is currently unclear how these endocannabinoid abnormalities relate to metabolic changes in psychosis. Here we review recent research in the field of metabolic co-morbidities in psychotic disorders as well as the methods to study them and potential links to the endocannabinoid system. We also describe the bioinformatics platforms developed in the EU project METSY for the investigations of the biological etiology in patients at risk of psychosis and in first episode psychosis patients. The METSY project was established with the aim to identify and evaluate multi-modal peripheral and neuroimaging markers that may be able to predict the onset and prognosis of psychiatric and metabolic symptoms in patients at risk of developing psychosis and first episode psychosis patients. Given the intrinsic complexity and widespread role of lipid metabolism, a systems biology approach which combines molecular, structural and functional neuroimaging methods with detailed metabolic characterisation and multi-variate network analysis is essential in order to identify how lipid dysregulation may contribute to psychotic disorders. A decision support system, integrating clinical, neuropsychological and neuroimaging data, was also developed in order to aid clinical decision making in psychosis. Knowledge of common and specific mechanisms may aid the etiopathogenic understanding of psychotic and metabolic disorders, facilitate early disease detection, aid treatment selection and elucidate new targets for pharmacological treatments.
The Toarcian Oceanic Anoxic Event (T-OAE, c. 182 Ma) represents a major perturbation of the carbon cycle marked by widespread black shale deposition. Consequently, the onset of the T-OAE has been linked to the combined effects of global warming, high productivity, basin restriction and salinity stratification. However, the processes that led to termination of the event remain elusive. Here, we present palynological data from Arctic Siberia (Russia), the Viking Corridor (offshore Norway) and the Yorkshire Coast (UK), all spanning the upper Pliensbachian – upper Toarcian stages. Rather than a ‘dinoflagellate cyst black-out’, as recorded in T-OAE strata of NW Europe, both the Arctic and Viking Corridor records show high abundance and dinoflagellate diversity throughout the T-OAE interval as calibrated by C-isotope records. Significantly, in the Arctic Sea and Viking Corridor, numerous species of the Parvocysta and Phallocysta suites make their first appearance in the lower Toarcian Falciferum Zone much earlier than in Europe, where these key dinoflagellate species appeared suddenly during the Bifrons Zone. Our results indicate migrations of Arctic dinoflagellate species, driven by relative sea-level rise in the Viking Corridor and the establishment of a S-directed circulation from the Arctic Sea into the Tethys Ocean. The results support oceanographic models, but are at odds with some interpretations based on geochemical proxies. The migration of Arctic dinoflagellate species coincides with the end of the T-OAE and marks the arrival of oxygenated, low-salinity Arctic waters, triggering a regime change from persistent euxinia to more dynamic oxygen conditions.
Genetic evaluation of Piétrain sires in Flanders occurs under standardized conditions, on test stations with fixed dam breeds, standardized diets and uniform management practices. As environmental conditions vary on commercial farms and differ from the test stations, this study aimed at understanding to what extent the sire, the dam breed and the interaction between both affects the translation of breeding values to practice. Dams of two commercial breeds were inseminated with semen from one of five different sires selected for contrasting breeding values (daily gain, feed conversion ratio and carcass quality). For each sire by dam breed combination, six pen replicates (with three gilts and three barrows per pen) were evaluated for growth performance from 9 weeks of age (20 kg) to slaughter (110 kg), and for carcass and meat quality. In our experimental setup, both sire and dam breed affected growth, carcass and meat quality traits. No significant sire×dam breed interactions on performance could be detected. Though a tendency for interaction on average daily feed intake between 20 and 110 kg (P=0.087), and on pork colour (lightness) (P=0.093) was present. In general, offspring of all tested sires behaved similarly in both dam breeds, indicating that estimated breeding values for Piétrain sires determined in one dam breed are representative in other dam breeds as well.
Eight ruminally-fistulated wethers were used to examine the temporal effects of afternoon (PM; 1600h) v. morning (AM; 0800 h) allocation of fresh spring herbage from a perennial ryegrass (Lolium perenne L.)-based pasture on fermentation and microbial community dynamics. Herbage chemical composition was minimally affected by time of allocation, but daily mean ammonia concentrations were greater for the PM group. The 24-h pattern of ruminal fermentation (i.e. time of sampling relative to time of allocation), however, varied considerably for all fermentation variables (P⩽0.001). Most notably amongst ruminal fermentation characteristics, ammonia concentrations showed a substantial temporal variation; concentrations of ammonia were 1.7-, 2.0- and 2.2-fold greater in rumens of PM wethers at 4, 6 and 8h after allocation, respectively, compared with AM wethers. The relative abundances of archaeal and ciliate protozoal taxa were similar across allocation groups. In contrast, the relative abundances of members of the rumen bacterial community, like Prevotella 1 (P=0.04), Bacteroidales RF16 group (P=0.005) and Fibrobacter spp. (P=0.008) were greater for the AM group, whereas the relative abundance of Kandleria spp. was greater (P=0.04) for the PM group. Of these taxa, only Prevotella 1 (P=0.04) and Kandleria (P<0.001) showed a significant interaction between time of allocation and time of sampling relative to feed allocation. Relative abundances of Prevotella 1 were greater at 2h (P=0.05), 4h (P=0.003) and 6h (P=0.01) after AM allocation of new herbage, whereas relative abundances of Kandleria were greater at 2h (P=0.003) and 4h (P<0.001) after PM allocation. The early post-allocation rise in ammonia concentrations in PM rumens occurred simultaneously with sharp increases in the relative abundance of Kandleria spp. and with a decline in the relative abundance of Prevotella. All measures of fermentation and most microbial community composition data showed highly dynamic changes in concentrations and genus abundances, respectively, with substantial temporal changes occurring within the first 8h of allocating a new strip of herbage. The dynamic changes in the relative abundances of certain bacterial groups, in synchrony with a substantial diurnal variation in ammonia concentrations, has potential effects on the efficiency by which N is utilised by the grazing ruminant.
To assess hospital surgical-site infection (SSI) identification and reporting following colon surgery and abdominal hysterectomy via a statewide external validation
Infection preventionists (IPs) from the California Department of Public Health (CDPH) performed on-site SSI validation for surgical procedures performed in hospitals that voluntarily participated. Validation involved chart review of SSI cases previously reported by hospitals plus review of patient records flagged for review by claims codes suggestive of SSI. We assessed the sensitivity of traditional surveillance and the added benefit of claims-based surveillance. We also evaluated the positive predictive value of claims-based surveillance (ie, workload efficiency).
Upon validation review, CDPH IPs identified 239 SSIs following colon surgery at 42 hospitals and 76 SSIs following abdominal hysterectomy at 34 hospitals. For colon surgery, traditional surveillance had a sensitivity of 50% (47% for deep incisional or organ/space [DI/OS] SSI), compared to 84% (88% for DI/OS SSI) for claims-based surveillance. For abdominal hysterectomy, traditional surveillance had a sensitivity of 68% (67% for DI/OS SSI) compared to 74% (78% for DI/OS SSI) for claims-based surveillance. Claims-based surveillance was also efficient, with 1 SSI identified for every 2 patients flagged for review who had undergone abdominal hysterectomy and for every 2.6 patients flagged for review who had undergone colon surgery. Overall, CDPH identified previously unreported SSIs in 74% of validation hospitals performing colon surgery and 35% of validation hospitals performing abdominal hysterectomy.
Claims-based surveillance is a standardized approach that hospitals can use to augment traditional surveillance methods and health departments can use for external validation.
There is a commitment by the European pig sector to ban surgical castration of male piglets in the European Union in 2018. One alternative to castration is to raise entire male pigs, with an increased risk of boar taint. A field study was performed to: (1) evaluate inter- and intra-farm variation in boar taint prevalence, (2) investigate factors measured at slaughter influencing boar taint and (3) evaluate the relationship between sensorial scoring by a trained panel and the concentration of boar taint components. From 34 farms, neck fat samples were collected from all entire male pigs in at least two slaughter batches per farm (78 batches; 9167 animals). In addition to olfactory boar taint analysis, data were also collected on fresh skin lesions (score 0 to 3) at the slaughter line, slaughter weight, lean meat percentage, duration of transport, time spent in lairage, total delivery duration, day length, shortening of days and outdoor mean temperature. Using the hot iron method, neck fat samples were scored (eight-point scale) for boar taint. Average boar taint prevalence (score ≥3) was 5.6±2.5% and the mean difference between the maximum and minimum prevalence per farm was 4.3±3.2%. Androstenone (AND), skatole (SKA) and indole concentrations were measured for a subset (n=254) of the samples. According to binomial univariate mixed models, entire male pigs with a higher skin lesion score had higher odds of having boar taint (P=0.031), as did fatter entire male pigs (P<0.001). In the binomial multivariate mixed model lean meat percentage (P<0.001) and outdoor mean temperature (P=0.005) remained as only significant factors. Based on our results, we can conclude that these statistically significant at least partially influence the prevalence of boar taint. According to the binomial univariate mixed models SKA concentration in liquid fat seems a better predictor for boar taint than AND. There were no significant synergetic effects between boar taint compounds.
Maternal prenatal stress during pregnancy is associated with fetal growth restriction and adverse neurodevelopmental outcomes, which may be mediated by impaired placental function. Imprinted genes control fetal growth, placental development, adult behaviour (including maternal behaviour) and placental lactogen production. This study examined whether maternal prenatal depression was associated with aberrant placental expression of the imprinted genes paternally expressed gene 3 (PEG3), paternally expressed gene 10 (PEG10), pleckstrin homology-like domain family a member 2 (PHLDA2) and cyclin-dependent kinase inhibitor 1C (CDKN1C), and resulting impaired placental human placental lactogen (hPL) expression.
A diagnosis of depression during pregnancy was recorded from Manchester cohort participants’ medical notes (n = 75). Queen Charlotte's (n = 40) and My Baby and Me study (MBAM) (n = 81) cohort participants completed the Edinburgh Postnatal Depression Scale self-rating psychometric questionnaire. Villous trophoblast tissue samples were analysed for gene expression.
In a pilot study, diagnosed depression during pregnancy was associated with a significant reduction in placental PEG3 expression (41%, p = 0.02). In two further independent cohorts, the Queen Charlotte's and MBAM cohorts, placental PEG3 expression was also inversely associated with maternal depression scores, an association that was significant in male but not female placentas. Finally, hPL expression was significantly decreased in women with clinically diagnosed depression (44%, p < 0.05) and in those with high depression scores (31% and 21%, respectively).
This study provides the first evidence that maternal prenatal depression is associated with changes in the placental expression of PEG3, co-incident with decreased expression of hPL. This aberrant placental gene expression could provide a possible mechanistic explanation for the co-occurrence of maternal depression, fetal growth restriction, impaired maternal behaviour and poorer offspring outcomes.
Remains of elasmosaurid plesiosaurs are exceedingly rare in the type-Maastrichtian strata (Late Cretaceous, southeast Netherlands and northeast Belgium), in stark contrast to relatively common skeletal remains of mosasaurs. Here, we present an analysis of δ13C stable isotope values for tooth enamel of two elasmosaur teeth from the type Maastrichtian. The δ13C signal is a proxy for foraging area, trophic level and diving behaviour, the net value of which in these rare elasmosaurs turns out to be not noticeably different from that for the much commoner mosasaurs in the type Maastrichtian. Therefore, the rarity of elasmosaurs in the area probably reflects a primary near-absence of such reptiles during the latest Cretaceous, rather than a taphonomic artefact.
Patients with psychosis display the so-called ‘Jumping to Conclusions’ bias (JTC) – a tendency for hasty decision-making in probabilistic reasoning tasks. So far, only a few studies have evaluated the JTC bias in ‘at-risk mental state’ (ARMS) patients, specifically in ARMS samples fulfilling ‘ultra-high risk’ (UHR) criteria, thus not allowing for comparisons between different ARMS subgroups.
In the framework of the PREVENT (secondary prevention of schizophrenia) study, a JTC task was applied to 188 patients either fulfilling UHR criteria or presenting with cognitive basic symptoms (BS). Similar data were available for 30 healthy control participants matched for age, gender, education and premorbid verbal intelligence. ARMS patients were identified by the Structured Interview for Prodromal Symptoms (SIPS) and the Schizophrenia Proneness Instrument – Adult Version (SPI-A).
The mean number of draws to decision (DTD) significantly differed between ARM -subgroups: UHR patients made significantly less draws to make a decision than ARMS patients with only cognitive BS. Furthermore, UHR patients tended to fulfil behavioural criteria for JTC more often than BS patients. In a secondary analysis, ARMS patients were much hastier in their decision-making than controls. In patients, DTD was moderately associated with positive and negative symptoms as well as disorganization and excitement.
Our data indicate an enhanced JTC bias in the UHR group compared to ARMS patients with only cognitive BS. This underscores the importance of reasoning deficits within cognitive theories of the developing psychosis. Interactions with the liability to psychotic transitions and therapeutic interventions should be unravelled in longitudinal studies.
Bone metabolism fluctuates throughout the reproductive cycle of sows to enable foetal growth and milk production. Although increased bone mineralisation is conceivable in sows during reproduction, a study of mineralisation in function of parity has not been performed. This study evaluated the fluctuations of markers for bone metabolism in primiparous and multiparous sows throughout a reproductive cycle. The experiment included ten multiparous and five primiparous commercial hybrid sows from one herd. The sows were monitored for one reproductive cycle and fed according to commercial dietary standards. Blood samples were taken in the morning before feeding at fixed time intervals before (day -5) and during gestation (insemination (day 0), 21, 42, 63, 84), around parturition (day 108, 112, parturition (115), 118), and during lactation (day 122, 129, 143). Serum osteocalcin (OC) concentration increased in early and mid-gestation (P=0.002) and decreased at the end of gestation (P=0.001), whereas crosslaps (CTX) concentration decreased during early and mid-gestation (P=0.002) and increased towards the end of gestation (P=0.001). Towards the end of lactation serum levels of both markers increased (P=0.007 and 0.013, respectively). For hydroxyproline (HYP) no significant fluctuation in function of the reproductive cycle was detected. Matrix metalloproteinase 2 (MMP2) concentration increased towards parturition for both primiparous and multiparous sows (P=0.001), whereas during lactation no significant fluctuations in function of the reproductive cycle were found. A parity effect was found for OC and CTX (P<0.010), but not for the other markers. These results demonstrate that bone metabolism differed between primiparous and multiparous sows, although in both groups a similar fluctuation throughout the reproductive cycle was observed.
Sows housed in groups have to move through their pen to fulfil their behavioural and physiological needs such as feeding and resting. In addition to causing pain and discomfort, lameness may restrict the ability of sows to fulfil such needs. The aim of our study was to investigate the extent to which the mobility of sows is affected by different degrees of lameness. Mobility was measured as the sow’s willingness or capability to cover distances. Feed-restricted hybrid sows with different gait scores were subjected to a feed reward collection test in which they had to walk distances to obtain subsequent rewards. In all, 29 group-housed sows at similar gestation stage (day 96.6±7 s.d.) were visually recorded for gait and classified as non-lame, mildly lame, moderately lame or severely lame. All sows received 2.6 kg of standard commercial gestation feed per day. The test arena consisted of two feeding locations separated from each other by a Y-shaped middle barrier. Feed rewards were presented at the two feeders in turn, using both light and sound cues to signal the availability of a new feed reward. Sows were individually trained during 5 non-consecutive days for 10 min/day with increasing barrier length (range: 0 to 3.5 m) each day. After training, sows were individually tested once per day on 3 non-consecutive days with the maximum barrier length such that they had to cover 9.3 m to walk from one feeder to the other. The outcome variable was the number of rewards collected in a 15-min time span. Non-lame and mildly lame sows obtained more rewards than moderately lame and severely lame sows (P<0.01). However, no significant difference was found between non-lame and mildly lame sows (P=0.69), nor between moderately lame and severely lame sows (P=1.00). This feed reward collection test indicates that both moderately lame and severely lame sows are limited in their combined ability and willingness to walk, but did not reveal an effect of mild lameness on mobility. These findings suggest that moderately and more severely lame sows, but not mildly lame sows, might suffer from reduced access to valuable resources in group housing systems.