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Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.
The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.
There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.
Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
We evaluated whether a diagnostic stewardship initiative consisting of ASP preauthorization paired with education could reduce false-positive hospital-onset (HO) Clostridioides difficile infection (CDI).
Single center, quasi-experimental study.
Tertiary academic medical center in Chicago, Illinois.
Adult inpatients were included in the intervention if they were admitted between October 1, 2016, and April 30, 2018, and were eligible for C. difficile preauthorization review. Patients admitted to the stem cell transplant (SCT) unit were not included in the intervention and were therefore considered a contemporaneous noninterventional control group.
The intervention consisted of requiring prescriber attestation that diarrhea has met CDI clinical criteria, ASP preauthorization, and verbal clinician feedback. Data were compared 33 months before and 19 months after implementation. Facility-wide HO-CDI incidence rates (IR) per 10,000 patient days (PD) and standardized infection ratios (SIR) were extracted from hospital infection prevention reports.
During the entire 52 month period, the mean facility-wide HO-CDI-IR was 7.8 per 10,000 PD and the SIR was 0.9 overall. The mean ± SD HO-CDI-IR (8.5 ± 2.0 vs 6.5 ± 2.3; P < .001) and SIR (0.97 ± 0.23 vs 0.78 ± 0.26; P = .015) decreased from baseline during the intervention. Segmented regression models identified significant decreases in HO-CDI-IR (Pstep = .06; Ptrend = .008) and SIR (Pstep = .1; Ptrend = .017) trends concurrent with decreases in oral vancomycin (Pstep < .001; Ptrend < .001). HO-CDI-IR within a noninterventional control unit did not change (Pstep = .125; Ptrend = .115).
A multidisciplinary, multifaceted intervention leveraging clinician education and feedback reduced the HO-CDI-IR and the SIR in select populations. Institutions may consider interventions like ours to reduce false-positive C. difficile NAAT tests.
Conservation resources are limited, yet an increasing number of species are under threat. Assessing species for their conservation needs is, therefore, a vital first step in identifying and prioritizing species for both ex situ and in situ conservation actions. Using a transparent, logical and objective method, the Conservation Needs Assessment process developed by Amphibian Ark uses current knowledge of species in the wild to determine those with the most pressing conservation needs, and provides a foundation for the development of holistic conservation action plans that combine in situ and ex situ actions as appropriate. These assessments allow us to maximize the impact of limited conservation resources by identifying which measures could best serve those species requiring help. The Conservation Needs Assessment complements the IUCN Red List assessment, and together they provide a more holistic guide to conservation priorities and actions. Conservation Needs Assessments generate national prioritized lists of species recommended for conservation action. These can subsequently be used to assist in the development of species recovery plans and national action plans, or to inform national conservation priorities better. Additional tools that will evaluate the recommendations for ex situ rescues, to determine the best candidates for conservation breeding programmes, are currently under development.
The pepper weevil, Anthonomus eugenii Cano (Coleoptera: Curculionidae), is the most important pest of pepper (Capsicum Linnaeus; Solanaceae) crops in North America. Native to Mexico, the southern United States of America, and Central America, it is intercepted in Canada when peppers are imported to supplement domestic production. Given the proximity of greenhouse and field production to packing facilities, this pest poses a serious risk to the cultivation of peppers in Canada. Once established, it is difficult to control because immature stages of the weevil are protected within the pepper fruit. As such, chemical control targeting these life stages is not effective, and other strategies, including biological control, may prove useful. To explore the potential for biological control options to manage the pepper weevil in areas at risk in Canada, natural enemy surveys were conducted in southern Ontario following the reports of transient, localised field populations in 2016. Parasitoids belonging to three Hymenoptera families including Pteromalidae (Jaliscoa hunteri Crawford, Pteromalus anthonomi Ashmead), Eupelmidae (Eupelmus pulchriceps Cameron), and Braconidae (Nealiolus Mason species, Bracon Fabricius species) were reared from infested field-collected pepper fruits. Together, these new natural enemy records could facilitate the exploration and development of novel agents for the biological control of the pepper weevil.
The content of omega-3 long-chain polyunsaturated fatty acids (n−3 LCPUFA) in chicken meat can be boosted by feeding broilers a diet containing α-linolenic acid (ALA, from flaxseed oil), some of which is converted by hepatic enzymes to n−3 LCPUFA. However, most of the accumulated n−3 polyunsaturated fatty acid (PUFA) in meat tissues is still in the form of ALA. Despite this, the levels of chicken diets are being enhanced by the inclusion of vegetable and marine sources of omega-3 fats. This study investigated whether the capacity of chicken for n−3 LCPUFA accumulation could be enhanced or inhibited by exposure to an increased supply of ALA or n−3 LCPUFA in ovo. Breeder hens were fed either flaxseed oil (High-ALA), fish oil (high n−3 LCPUFA) or tallow- (low n−3 PUFA, Control) based diets. The newly hatched chicks in each group were fed either the High-ALA or the Control diets until harvest at 42 days’ post-hatch. The n−3 PUFA content of egg yolk and day-old chick meat closely matched the n−3 PUFA composition of the maternal diet. In contrast, the n−3 PUFA composition of breast and leg meat tissues of the 42-day-old offspring closely matched the diet fed post-hatch, with no significant effect of maternal diet. Indeed, there was an inhibition of n−3 LCPUFA accumulation in meat of the broilers from the maternal Fish-Oil diet group when fed the post-hatch High-ALA diet. Therefore, this approach is not valid to elevate n-3 LCPUFA in chicken meat.
Aberrant microbiota composition and function have been linked to several pathologies, including type 2 diabetes. In animal models, prebiotics induce favourable changes in the intestinal microbiota, intestinal permeability (IP) and endotoxaemia, which are linked to concurrent improvement in glucose tolerance. This is the first study to investigate the link between IP, glucose tolerance and intestinal bacteria in human type 2 diabetes. In all, twenty-nine men with well-controlled type 2 diabetes were randomised to a prebiotic (galacto-oligosaccharide mixture) or placebo (maltodextrin) supplement (5·5 g/d for 12 weeks). Intestinal microbial community structure, IP, endotoxaemia, inflammatory markers and glucose tolerance were assessed at baseline and post intervention. IP was estimated by the urinary recovery of oral 51Cr-EDTA and glucose tolerance by insulin-modified intravenous glucose tolerance test. Intestinal microbial community analysis was performed by high-throughput next-generation sequencing of 16S rRNA amplicons and quantitative PCR. Prebiotic fibre supplementation had no significant effects on clinical outcomes or bacterial abundances compared with placebo; however, changes in the bacterial family Veillonellaceae correlated inversely with changes in glucose response and IL-6 levels (r −0·90, P=0·042 for both) following prebiotic intake. The absence of significant changes to the microbial community structure at a prebiotic dosage/length of supplementation shown to be effective in healthy individuals is an important finding. We propose that concurrent metformin treatment and the high heterogeneity of human type 2 diabetes may have played a significant role. The current study does not provide evidence for the role of prebiotics in the treatment of type 2 diabetes.
Prebiotic oligosaccharides have the ability to generate important changes in the gut microbiota composition that may confer health benefits to the host. Reducing the impurities in prebiotic mixtures could expand their applications in food industries and improve their selectivity and prebiotic effect on the potential beneficial bacteria such as bifidobacteria and lactobacilli. This study aimed to determine the in vitro potential fermentation properties of a 65 % galacto-oligosaccharide (GOS) content Bimuno® GOS (B-GOS) on gut microbiota composition and their metabolites. Fermentation of 65 % B-GOS was compared with 52 % B-GOS in pH- and volume-controlled dose–response anaerobic batch culture experiments. In total, three different doses (1, 0·5 and 0·33 g equivalent to 0·1, 0·05 and 0·033 g/l) were tested. Changes in the gut microbiota during a time course were identified by fluorescence in situ hybridisation, whereas small molecular weight metabolomics profiles and SCFA were determined by 1H-NMR analysis and GC, respectively. The 65 % B-GOS showed positive modulation of the microbiota composition during the first 8 h of fermentation with all doses. Administration of the specific doses of B-GOS induced a significant increase in acetate as the major SCFA synthesised compared with propionate and butyrate concentrations, but there were no significant differences between substrates. The 65 % B-GOS in syrup format seems to have, in all the analysis, an efficient prebiotic effect. However, the applicability of such changes remains to be shown in an in vivo trial.
Background: In British Columbia, neuromuscular disease accounts for 31% of IVIg use, at a cost of $10.1 M. In addition to the new screening pathway, the BC Neuromuscular IVIg Program developed the Chronic High User Project to identify areas for improvement in utilization. Methods: Utilizing CTR data, all patients on IVIg maintenance therapy for approved neuromuscular conditions between April 1, 2013 and March 31, 2014 were identified. Patients receiving higher than usual IVIG treatments (CIDP and MG >1110 grams/year, MMNCB > 1400 grams/year) were evaluated. Following panel review, utilization data was compared with a second cohort (2014 to 2015) to determine impact. Following review, appropriateness of treatment was determined by consensus from a 3-member panel, and recommendations were made. Results: Of 377 patients, 38 “High Users” were identified. 29 cases were determined to be appropriate; 9 were not. There was a reduction in mean grams/episode in CIDP (1135g to 990g) and MG (1099 g to 1022g) between cohorts. The mean grams/episode for MMNCB did not change. Conclusions: In specific cases, the IVIg High User Program identified patients in whom the treatment could be optimized. However, the vast majority of use of IVIg for Neuromuscular Disease in BC is appropriate, including in patients requiring higher that “usual” doses.
We summarize the results obtained from our suite of chemical evolution models for spiral disks, computed for different total masses and star formation efficiencies. Once the gas, stars and star formation radial distributions are reproduced, we analyze the Oxygen abundances radial profiles for gas and stars, in addition to stellar averaged ages and global metallicity. We examine scenarios for the potential origin of the apparent flattening of abundance gradients in the outskirts of disk galaxies, in particular the role of molecular gas formation prescriptions.
It is recognised that ageing induces various changes to the human colonic microbiota. Most relevant is a reduction in bifidobacteria, which is a health-positive genus. Prebiotics, such as galacto-oligosaccharides (GOS), are dietary ingredients that selectively fortify beneficial gut microbial groups. Therefore, they have the potential to reverse the age-related decline in bifidobacteria and modulate associated health parameters. We assessed the effect of GOS mixture (Bimuno (B-GOS)) on gut microbiota, markers of immune function and metabolites in forty elderly (age 65–80 years) volunteers in a randomised, double-blind, placebo (maltodextrin)-controlled, cross-over study. The intervention periods consisted of 10 weeks with daily doses of 5·5 g/d with a 4-week washout period in between. Blood and faecal samples were collected for the analyses of faecal bacterial populations and immune and metabolic biomarkers. B-GOS consumption led to significant increases in bacteroides and bifidobacteria, the latter correlating with increased lactic acid in faecal waters. Higher IL-10, IL-8, natural killer cell activity and C-reactive protein and lower IL-1β were also observed. Administration of B-GOS to elderly volunteers may be useful in positively affecting the microbiota and some markers of immune function associated with ageing.
A segment of the debate surrounding the commercialization and use of glyphosate-resistant (GR) crops focuses on the theory that the implementation of these traits is an extension of the intensification of agriculture that will further erode the biodiversity of agricultural landscapes. A large field-scale study was initiated in 2006 in the United States on 156 different field sites with a minimum 3-yr history of GR-corn, -cotton or -soybean in the cropping system. The impact of cropping system, crop rotation, frequency of using the GR crop trait, and several categorical variables on seedbank weed population density and diversity was analyzed. The parameters of total weed population density of all species in the seedbank, species richness, Shannon's H′ and evenness were not affected by any management treatment. The similarity between the seedbank and aboveground weed community was more strongly related to location than management; previous year's crops and cropping systems were also important while GR trait rotation was not. The composition of the weed flora was more strongly related to location (geography) than any other parameter. The diversity of weed flora in agricultural sites with a history of GR crop production can be influenced by several factors relating to the specific method in which the GR trait is integrated (cropping system, crop rotation, GR trait rotation), the specific weed species, and the geographical location. Continuous GR crop, compared to fields with other cropping systems, only had greater species diversity (species richness) of some life forms, i.e., biennials, winter annuals, and prostrate weeds. Overall diversity was related to geography and not cropping system. These results justify further research to clarify the complexities of crops grown with herbicide-resistance traits to provide a more complete characterization of their culture and local adaptation to the weed seedbank.
Coffee is a relatively rich source of chlorogenic acids (CGA), which, as other polyphenols, have been postulated to exert preventive effects against CVD and type 2 diabetes. As a considerable proportion of ingested CGA reaches the large intestine, CGA may be capable of exerting beneficial effects in the large gut. Here, we utilise a stirred, anaerobic, pH-controlled, batch culture fermentation model of the distal region of the colon in order to investigate the impact of coffee and CGA on the growth of the human faecal microbiota. Incubation of coffee samples with the human faecal microbiota led to the rapid metabolism of CGA (4 h) and the production of dihydrocaffeic acid and dihydroferulic acid, while caffeine remained unmetabolised. The coffee with the highest levels of CGA (P< 0·05, relative to the other coffees) induced a significant increase in the growth of Bifidobacterium spp. relative to the control vessel at 10 h after exposure (P< 0·05). Similarly, an equivalent quantity of CGA (80·8 mg, matched with that in high-CGA coffee) induced a significant increase in the growth of Bifidobacterium spp. (P< 0·05). CGA alone also induced a significant increase in the growth of the Clostridium coccoides–Eubacteriumrectale group (P< 0·05). This selective metabolism and subsequent amplification of specific bacterial populations could be beneficial to host health.
This placebo-controlled, randomised, double-blind, cross-over human feeding study aimed to determine the prebiotic effect of agave fructans. A total of thirty-eight volunteers completed this trial. The treatment consisted of 3 weeks' supplementation with 5 g/d of prebiotic agave fructan (Predilife) or equivalent placebo (maltodextrin), followed by a 2-week washout period following which subjects were crossed over to alternate the treatment arm for 3 weeks followed by a 2-week washout. Faecal samples were collected at baseline, on the last day of treatment (days 22 and 58) and washout (days 36 and 72), respectively. Changes in faecal bacterial populations, SCFA and secretory IgA were assessed using fluorescent in situ hybridisation, GC and ELISA, respectively. Bowel movements, stool consistencies, abdominal comfort and mood changes were evaluated by a recorded daily questionnaire. In parallel, the effect of agave fructans on different regions of the colon using a three-stage continuous culture simulator was studied. Predilife significantly increased faecal bifidobacteria (log10 9·6 (sd 0·4)) and lactobacilli (log10 7·7 (sd 0·8)) compared with placebo (log10 9·2 (sd 0·4); P = 0·00) (log10 7·4 (sd 0·7); P = 0·000), respectively. No change was observed for other bacterial groups tested, SCFA, secretory IgA, and PGE2 concentrations between the treatment and placebo. Denaturing gradient gel electrophoresis analysis indicated that bacterial communities were randomly dispersed and no significant differences were observed between Predilife and placebo treatments. The in vitro models showed similar increases in bifidobacterial and lactobacilli populations to that observed with the in vivo trial. To conclude, agave fructans are well tolerated in healthy human subjects and increased bifidobacteria and lactobacilli numbers in vitro and in vivo but did not influence other products of fermentation.