Potential impact of prickly pear cactus flour and Salix babylonica extract on cecal fermentation and methane production in horses

The cecal gas (GP) and methane (CH4) production and cecal fermentation kinetics when corn grain (CG) was replaced with prickly cactus (PC) in a horse’s diet at different levels of Salix babylonica (SB) extract was investigated. Three total mixed rations where CG was replaced with PC at three levels (/kg): 0 g (Control), 75 g (PC75) or 150 g (PC150) were prepared and SB extract added at four levels: 0, 0.6, 1.2 and 1.8 mL/g dry matter (DM) of substrates. No ration type 9 SB extract dose interaction was observed (P [0.05) for GP kinetics and CH4 production. Increasing the level of PC in the ration quadratically increased (P \0.01) the asymptotic GP and decreased (P\0.01) the rate and lag time of GP. Increasing the level of PC in the ration, increased GP values (P\0.05). Increasing the level of SB extract linearly decreased (P = 0.001) the lag time of GP of all diets without affecting the asymptotic GP or the rate of GP. Ration type and SB level had no effect (P [0.05) on CH4 production; however, at 36 h of incubation, SB extract decreased CH4 production. The rations PC75 and PC150 increased cecal pH compared with the control ration. The PC150 ration had the highest (P\0.05) DM degradability, short chain fatty acids production, and gas yield after 24 h of incubation, with no effect (P[0.05) of SB inclusion on all investigated fermentation kinetic parameters. It is concluded that increasing the level of PC in the diet of horse and replacing CG up to 60%, increased GP and improved cecal fermentation kinetics without affecting CH4 production. Inclusion of S. babylonica extract in the tested rations had weak effects on fermentation kinetics although it decreased the lag time of GP

A consensus-based framework for conducting and reporting osteoarthritis phenotype research

Background The concept of osteoarthritis (OA) heterogeneity is evolving and gaining renewed interest. According to this concept, distinct subtypes of OA need to be defined that will likely require recognition in research design and different approaches to clinical management. Although seemingly plausible, a wide range of views exist on how best to operationalize this concept. The current project aimed to provide consensus-based definitions and recommendations that together create a framework for conducting and reporting OA phenotype research. Methods A panel of 25 members with expertise in OA phenotype research was composed. First, panel members participated in an online Delphi exercise to provide a number of basic definitions and statements relating to OA phenotypes and OA phenotype research. Second, panel members provided input on a set of recommendations for reporting on OA phenotype studies. Results Four Delphi rounds were required to achieve sufficient agreement on 11 definitions and statements. OA phenotypes were defined as subtypes of OA that share distinct underlying pathobiological and pain mechanisms and their structural and functional consequences. Reporting recommendations pertaining to the study characteristics, study population, data collection, statistical analysis, and appraisal of OA phenotype studies were provided. Conclusions This study provides a number of consensus-based definitions and recommendations relating to OA phenotypes. The resulting framework is intended to facilitate research on OA phenotypes and increase combined efforts to develop effective OA phenotype classification. Success in this endeavor will hopefully translate into more effective, differentiated OA management that will benefit a multitude of OA patients

Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial

Background Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. Method We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants were randomly assigned (1:1) using a centralised validated computer program, to temporarily suspend methotrexate treatment for 2 weeks immediately after COVID-19 booster vaccination or continue treatment as usual. The primary outcome was S1-RBD antibody titres 4 weeks after COVID-19 booster vaccination and was assessed masked to group assignment. All randomly assigned patients were included in primary and safety analyses. This trial is registered with ISRCTN, ISRCTN11442263; following a pre-planned interim analysis, recruitment was stopped early. Finding Between Sept 30, 2021, and March 7, 2022, we screened 685 individuals, of whom 383 were randomly assigned: to either suspend methotrexate (n=191; mean age 58·8 years [SD 12·5], 118 [62%] women and 73 [38%] men) or to continue methotrexate (n=192; mean age 59·3 years [11·9], 117 [61%] women and 75 [39%] men). At 4 weeks, the geometric mean S1-RBD antibody titre was 25 413 U/mL (95% CI 22 227–29 056) in the suspend methotrexate group and 12 326 U/mL (10 538–14 418) in the continue methotrexate group with a geometric mean ratio (GMR) of 2·08 (95% CI 1·59–2·70; p<0·0001). No intervention-related serious adverse events occurred. Interpretation 2-week interruption of methotrexate treatment in people with immune-mediated inflammatory diseases enhanced antibody responses after COVID-19 booster vaccination that were sustained at 12 weeks and 26 weeks. There was a temporary increase in inflammatory disease flares, mostly self-managed. The choice to suspend methotrexate should be individualised based on disease status and vulnerability to severe outcomes from COVID-19. Funding National Institute for Health and Care Research

Cancer incidence in kidney transplant recipients: a study protocol

<p>Abstract</p> <p>Background</p> <p>Different publications show an increased incidence of neoplasms in renal transplant patients. The objective of this study is to determine the incidence of cancer in the recipients of renal transplants performed in the A Coruña Hospital (Spain) during the period 1981–2007.</p> <p>Methods/Design</p> <p>During the study period 1967 kidney transplants were performed, corresponding to 1710 patients. Patients with neoplasms prior to the transplant will be excluded (n = 38). A follow-up study was carried out in order to estimate cancer incidence after transplantation.</p> <p>For each patient, information included donor and recipient characteristics, patients and graft survival and cancer incidence after transplantation. Incident cancer is considered as new cases of cancer after the transplant with anatomopathological confirmation. Their location will be classified according to the ICD-9.</p> <p>The analysis will be calculated using the indirect standardisation method. Age-adjusted cancer incidence rates in the Spanish general population will be obtained from the Carlos III Health Institute, the National Epidemiology Centre of the Ministry of Science and Technology. Crude first, second and third-year post-transplantation cancer incidence rates will be calculated for male and female recipients. The number of cases of cancer at each site will be calculated from data in the clinical records. The expected number of cancers will be calculated from data supplied by the Carlos III Health Institute. For each tumour location we will estimate the standardized incidence ratios (SIRs), using sex-specific cancer incidence rates, by dividing the incidence rate for the transplant patients by the rate of the general population. The 95% confidence intervals of the SIRs and their associated p-values will be calculated by assuming that the observed cancers follow a Poisson distribution. Stratified analysis will be performed to examine the variation in the SIRs with sex and length of follow-up.</p> <p>Competing risk survival analysis methods will be applied to estimate the cumulative incidence of cancer and to identify variables associated to its occurrence.</p> <p>Discussion</p> <p>Information about cancer incidence in kidney transplant patients could be useful to adapt the guidelines on post-kidney transplant follow-up on tumour screening, and evaluate the impact of intervention measures for the prevention of cancer in these patients.</p

Do Author-Suggested Reviewers Rate Submissions More Favorably than Editor-Suggested Reviewers? A Study on Atmospheric Chemistry and Physics

Background: Ratings in journal peer review can be affected by sources of bias. The bias variable investigated here was the information on whether authors had suggested a possible reviewer for their manuscript, and whether the editor had taken up that suggestion or had chosen a reviewer that had not been suggested by the authors. Studies have shown that authorsuggested reviewers rate manuscripts more favorably than editor-suggested reviewers do. Methodology/Principal Findings: Reviewers ’ ratings on three evaluation criteria and the reviewers ’ final publication recommendations were available for 552 manuscripts (in total 1145 reviews) that were submitted to Atmospheric Chemistry and Physics, an interactive open access journal using public peer review (authors ’ and reviewers ’ comments are publicly exchanged). Public peer review is supposed to bring a new openness to the reviewing process that will enhance its objectivity. In the statistical analysis the quality of a manuscript was controlled for to prevent favorable reviewers ’ ratings from being attributable to quality instead of to the bias variable. Conclusions/Significance: Our results agree with those from other studies that editor-suggested reviewers rated manuscripts between 30 % and 42 % less favorably than author-suggested reviewers. Against this backdrop journal editors should consider either doing without the use of author-suggested reviewers or, if they are used, bringing in more than one editor-suggested reviewer for the review process (so that the review by author-suggested reviewers can be put i

Food-associated cues alter forebrain functional connectivity as assessed with immediate early gene and proenkephalin expression

<p>Abstract</p> <p>Background</p> <p>Cues predictive of food availability are powerful modulators of appetite as well as food-seeking and ingestive behaviors. The neurobiological underpinnings of these conditioned responses are not well understood. Monitoring regional immediate early gene expression is a method used to assess alterations in neuronal metabolism resulting from upstream intracellular and extracellular signaling. Furthermore, assessing the expression of multiple immediate early genes offers a window onto the possible sequelae of exposure to food cues, since the function of each gene differs. We used immediate early gene and proenkephalin expression as a means of assessing food cue-elicited regional activation and alterations in functional connectivity within the forebrain.</p> <p>Results</p> <p>Contextual cues associated with palatable food elicited conditioned motor activation and corticosterone release in rats. This motivational state was associated with increased transcription of the activity-regulated genes <it>homer1a</it>, <it>arc</it>, <it>zif268</it>, <it>ngfi-b </it>and c-<it>fos </it>in corticolimbic, thalamic and hypothalamic areas and of proenkephalin within striatal regions. Furthermore, the functional connectivity elicited by food cues, as assessed by an inter-regional multigene-expression correlation method, differed substantially from that elicited by neutral cues. Specifically, food cues increased cortical engagement of the striatum, and within the nucleus accumbens, shifted correlations away from the shell towards the core. Exposure to the food-associated context also induced correlated gene expression between corticostriatal networks and the basolateral amygdala, an area critical for learning and responding to the incentive value of sensory stimuli. This increased corticostriatal-amygdalar functional connectivity was absent in the control group exposed to innocuous cues.</p> <p>Conclusion</p> <p>The results implicate correlated activity between the cortex and the striatum, especially the nucleus accumbens core and the basolateral amygdala, in the generation of a conditioned motivated state that may promote excessive food intake. The upregulation of a number of genes in unique patterns within corticostriatal, thalamic, and hypothalamic networks suggests that food cues are capable of powerfully altering neuronal processing in areas mediating the integration of emotion, cognition, arousal, and the regulation of energy balance. As many of these genes play a role in plasticity, their upregulation within these circuits may also indicate the neuroanatomic and transcriptional correlates of extinction learning.</p

Visual Personal Familiarity in Amnestic Mild Cognitive Impairment

BACKGROUND: Patients with amnestic mild cognitive impairment are at high risk for developing Alzheimer's disease. Besides episodic memory dysfunction they show deficits in accessing contextual knowledge that further specifies a general concept or helps to identify an object or a person. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging, we investigated the neural networks associated with the perception of personal familiar faces and places in patients with amnestic mild cognitive impairment and healthy control subjects. Irrespective of stimulus type, patients compared to control subjects showed lower activity in right prefrontal brain regions when perceiving personally familiar versus unfamiliar faces and places. Both groups did not show different neural activity when perceiving faces or places irrespective of familiarity. CONCLUSIONS/SIGNIFICANCE: Our data highlight changes in a frontal cortical network associated with knowledge-based personal familiarity among patients with amnestic mild cognitive impairment. These changes could contribute to deficits in social cognition and may reduce the patients' ability to transition from basic to complex situations and tasks

NHR-49 Helps Germline-Less Worms Chew the Fat

In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of these processes is critical for germline-less animals to maintain their lipid stores and to sustain de novo fat synthesis during adulthood. Following germline ablation, NHR-49 is up-regulated in somatic cells by the conserved longevity determinants DAF-16/FOXO and TCER-1/TCERG1. Accordingly, NHR-49 overexpression in fertile animals extends their lifespan modestly. In fertile adults, nhr-49 expression is DAF-16/FOXO and TCER-1/TCERG1 independent although its depletion causes age-related lipid abnormalities. Our data provide molecular insights into how reproductive stimuli are integrated into global metabolic changes to alter the lifespan of the animal. They suggest that NHR-49 may facilitate the adaptation to loss of reproductive potential through synchronized enhancement of fatty-acid oxidation and desaturation, thus breaking down some fats ordained for reproduction and orchestrating a lipid profile conducive for somatic maintenance and longevity

Does Genetic Diversity Predict Health in Humans?

Genetic diversity, especially at genes important for immune functioning within the Major Histocompatibility Complex (MHC), has been associated with fitness-related traits, including disease resistance, in many species. Recently, genetic diversity has been associated with mate preferences in humans. Here we asked whether these preferences are adaptive in terms of obtaining healthier mates. We investigated whether genetic diversity (heterozygosity and standardized mean d2) at MHC and nonMHC microsatellite loci, predicted health in 153 individuals. Individuals with greater allelic diversity (d2) at nonMHC loci and at one MHC locus, linked to HLA-DRB1, reported fewer symptoms over a four-month period than individuals with lower d2. In contrast, there were no associations between MHC or nonMHC heterozygosity and health. NonMHC-d2 has previously been found to predict male preferences for female faces. Thus, the current findings suggest that nonMHC diversity may play a role in both natural and sexual selection acting on human populations