Sex differences in basal hypothalamic anorectic and orexigenic gene expression and the effect of quantitative and qualitative food restriction

Abstract Background Research into energy balance and growth has infrequently considered genetic sex, yet there is sexual dimorphism for growth across the animal kingdom. We test the hypothesis that in the chicken, there is a sex difference in arcuate nucleus neuropeptide gene expression, since previous research indicates hypothalamic AGRP expression is correlated with growth potential and that males grow faster than females. Because growth has been heavily selected in some chicken lines, food restriction is necessary to improve reproductive performance and welfare, but this increases hunger. Dietary dilution has been proposed to ameliorate this undesirable effect. We aimed to distinguish the effects of gut fullness from nutritional feedback on hypothalamic gene expression and its interaction with sex. Methods Twelve-week-old male and female fast-growing chickens were either released from restriction and fed ad libitum or a restricted diet plus 15% w/w ispaghula husk, a non-nutritive bulking agent, for 2 days. A control group remained on quantitative restriction. Hypothalamic arcuate nucleus neuropeptides were measured using real-time PCR. To confirm observed sex differences, the experiment was repeated using only ad libitum and restricted fed fast-growing chickens and in a genetically distinct breed of ad libitum fed male and female chickens. Linear mixed models (Genstat 18) were used for statistical analysis with transformation where appropriate. Results There were pronounced sex differences: expression of the orexigenic genes AGRP (P < 0.001) and NPY (P < 0.002) was higher in males of the fast-growing strain. In genetically distinct chickens, males had higher AGRP mRNA (P = 0.002) expression than females, suggesting sex difference was not restricted to a fast-growing strain. AGRP (P < 0.001) expression was significantly decreased in ad libitum fed birds but was high and indistinguishable between birds on a quantitative versus qualitative restricted diet. Inversely, gene expression of the anorectic genes POMC and CART was significantly higher in ad libitum fed birds but no consistent sex differences were observed. Conclusion Expression of orexigenic peptides in the avian hypothalamus are significantly different between sexes. This could be useful starting point of investigating further if AGRP is an indicator of growth potential. Results also demonstrate that gut fill alone does not reduce orexigenic gene expression

Personality profiles of cultures: aggregate personality traits

Personality profiles of cultures can be operationalized as the mean trait levels of culture members. College students from 51 cultures rated an individual from their country whom they knew well (N = 12, 156). Aggregate scores on Revised NEO Personality Inventory scales generalized across age and gender groups, approximated the individual-level Five-Factor Model, and correlated with aggregate self-report personality scores and other culture-level variables. Results were not attributable to national differences in economic development or to acquiescence. Geographical differences in scale variances and mean levels were replicated, with Europeans and Americans generally scoring higher in Extraversion than Asians and Africans. Findings support the rough scalar equivalence of NEO-PI-R factors and facets across cultures, and suggest that aggregate personality profiles provide insight into cultural differences

Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients

Objectives: To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of idiopathic inflammatory myopathy (IIM) patients. Methods: Adult patients with confirmed IIM recruited to the EuroMyositis registry (n = 1637) from four centres were investigated for the presence of MSAs/MAAs by radiolabelled-immunoprecipitation, with confirmation of anti-MDA5 and anti-NXP2 by ELISA. Clinical associations for each autoantibody were calculated for 1483 patients with a single or no known autoantibody by global linear regression modelling. Results: MSAs/MAAs were found in 61.5% of patients, with 84.7% of autoantibody positive patients having a sole specificity, and only three cases (0.2%) having more than one MSA. The most frequently detected autoantibody was anti-Jo-1 (18.7%), with a further 21 specificities each found in 0.2–7.9% of patients. Autoantibodies to Mi-2, SAE, TIF1, NXP2, MDA5, PMScl and the non-Jo-1 tRNA-synthetases were strongly associated (p < 0.001) with cutaneous involvement. Anti-TIF1 and anti-Mi-2 positive patients had an increased risk of malignancy (OR 4.67 and 2.50 respectively), and anti-SRP patients had a greater likelihood of cardiac involvement (OR 4.15). Interstitial lung disease was strongly associated with the anti-tRNA synthetases, antiMDA5, and anti-U1RNP/Sm. Overlap disease was strongly associated with anti-PMScl, anti-Ku, anti-U1RNP/Sm and anti-Ro60. Absence of MSA/MAA was negatively associated with extra-muscular manifestations. Conclusions: Myositis autoantibodies are present in the majority of patients with IIM and identify distinct clinical subsets. Furthermore, MSAs are nearly always mutually exclusive endorsing their credentials as valuable disease biomarkers

Increasing incidence of adult idiopathic inflammatory myopathies in the City of Salford, UK: A 10-year epidemiological study

Objectives. The aim was to identify and characterize all incident adult cases of idiopathic inflammatory myopathies (IIM) between 1 January 2007 and 31 December 2016 in the City of Salford, UK. / Methods. Adults first diagnosed with IIM within the study period were identified by: a Salford Royal NHS Foundation Trust (SRFT) inpatient episode IIM-specific ICD-10 coding search; all new patient appointments to SRFT neuromuscular outpatient clinics; and all Salford residents enrolled within the UKMYONET study. All patients with definite IIM by the 2017 EULAR/ACR classification criteria were included, as were probable cases if consensus expert opinion agreed. Cases were excluded if < 18 years of age at disease onset, if they did not meet probable criteria or when probable but expert opinion concluded a non-IIM diagnosis. / Results. The multimodal case ascertainment identified 1156 cases which, after review and application of exclusion criteria, resulted in 32 incident cases during the study period. Twenty-three of 32 were female, with a mean age of 58.1 years. The mean incidence of adult IIM was 17.6/1 000 000 person years, and higher for females than for males (25.2 vs 10.0/1 000 000 person years, respectively). A significant incidence increase over time was apparent (13.6 vs 21.4/1 000 000 person years; P=0.032). Using EULAR/ACR classification criteria, the largest IIM subtype (21/32) was PM, followed by DM (8/32), IBM (2/32) and amyopathic DM (1/32). Expert opinion subtype differed from EULAR/ACR classification criteria in 19/32 cases. / Conclusion. The incidence of adult IIM in Salford is 17.6/1 000 000 person years, higher in females, and is increasing over time. Disagreement exists between EULAR/ACR-derived and expert opinionderived IIM subtype assignments

AB0215 COMPARISON BETWEEN RITUXIMAB ORIGINATOR THERAPY AND ITS BIOSIMILAR IN THE INCIDENCE OF LATE-ONSET NEUTROPENIA IN ADULT PATIENTS WITH RHEUMATOID ARTHRITIS AND OTHER AUTOIMMUNE DISEASES

Background:Late-onset neutropenia (LON) occurs when the absolute neutrophil count drops below 1.5 × 10(9)/L four weeks after Rituximab infusion.1 It is a condition recognised more in haematological malignancy patients treated with Rituximab with a reported prevalence of 8% or higher.2 LON was reported in 6.5% of rheumatological patients1, while a French registry found a prevalence of 1.3% in rheumatoid arthritis patients.3Almost all patients receiving Rituximab originator therapy at our Rheumatology department were switched to its biosimilar starting from November 2017. Our haematology team observed LON cases in their patients after this period.Objectives:We wanted to establish whether there is increased LON occurrence with the biosimilar than the originator therapy, requiring specific monitoring.Methods:This is a cross-sectional retrospective review of 12 months period before and after switching to the biosimilar of all patients who received Rituximab for the first time. We reviewed the patients’ blood monitoring for up to 12 months after receiving Rituximab. We used a proforma to collect the age, sex, diagnosis, date of the first infusion, use of other DMARDs, LON occurrence within 12 months after the infusion and neutropenia within the 12 months before it in addition to the frequency of the blood monitoring after the infusion.Results:For the originator, between 1/1/2016 and 31/12/2016, 142 patients received Rituximab, 47 (33.09%) of them were given the treatment for the first time. Their median age was 62 years, 28 (59.5%) were females. The most common diagnosis was rheumatoid arthritis 38 (80.8%), and 35 (74.4%) patients were on other disease-modifying agents (DMARDs). Two patients (4.2%) developed LON. In both patients, this occurred during admission for septic arthritis whilst on antibiotics, and both had Grade 2: ≥1,000– &lt; 1,500/mm3 neutropenia.For the Biosimilar cohort, between 1/4/2019 and 31/3/2020, 161 patients received Rituximab, 36 (22.3%) of them were given the treatment for the first time. Their median age was 59 years, 27 (75%) of them were females. The most common diagnosis was rheumatoid arthritis 25 (69.4%), and 26 (72.2%) were on other DMARDs. One patient (2.77%) developed grade 2 LON one month after Rituximab. Another patient with known autoimmune neutropenia was excluded. In all the Three patients with LON in both groups, neutrophil count recovered in less than a month, and they had normal IgG before the infusion.The frequency of blood monitoring after Rituximab infusion was done 1-3 monthly in 32 (68%) patients and 23 (63.8%) patients in the originator and biosimilar groups, respectively.Four (8.5%) patients and three (8.3%) patients in the originator and biosimilar groups respectively had a frequency of blood monitoring done less than six-monthly.Conclusion:In our patients’ cohort, LON incidence following switching to the Rituximab biosimilar was not higher than the originator therapy.References:[1]Monaco, W. E., Jones, J. D. &amp; Rigby, W. F. C. Rituximab associated late-onset neutropenia-a rheumatology case series and review of the literature. Clin Rheumatol35, 2457–2462 (2016).[2]Dunleavy, K., Tay, K. &amp; Wilson, W. H. Rituximab-Associated Neutropenia. Seminars in Hematology47, 180–186 (2010).[3]Salmon, J. H. et al. Late-onset neutropenia after treatment with Rituximab for rheumatoid arthritis and other autoimmune diseases: data from the AutoImmunity and Rituximab registry. RMD Open1, e000034 (2015).Acknowledgements:The authors would like to thank pharmacist Christine Hay for her help in providing the Rituximab databases.Disclosure of Interests:Mostafa Meshaal Ahmad: None declared, Euan McRorie Speakers bureau: I have spoken at meetings sponsored by Roche several years ago, Consultant of: I have sat on advisory boards for Roche several years ago., Grant/research support from: I was the local investigator for the ORBIT study, published in the Lancet in 2016.</jats:sec

Understanding the Physics of Functional Fibers in the Gastrointestinal Tract: An Evidence-Based Approach to Resolving Enduring Misconceptions about Insoluble and Soluble Fiber

AbstractEnduring misconceptions about the physical effects of fiber in the gut have led to misunderstandings about the health benefits attributable to insoluble and soluble fiber. This review will focus on isolated functional fibers (eg, fiber supplements) whose effects on clinical outcomes have been readily assessed in well-controlled clinical studies. This review will also focus on three health benefits (cholesterol lowering, improved glycemic control, and normalizing stool form [constipation and diarrhea]) for which reproducible evidence of clinical efficacy has been published. In the small bowel, clinically meaningful health benefits (eg, cholesterol lowering and improved glycemic control) are highly correlated with the viscosity of soluble fibers: high viscosity fibers (eg, gel-forming fibers such as b-glucan, psyllium, and raw guar gum) exhibit a significant effect on cholesterol lowering and improved glycemic control, whereas nonviscous soluble fibers (eg, inulin, fructooligosaccharides, and wheat dextrin) and insoluble fibers (eg, wheat bran) do not provide these viscosity-dependent health benefits. In the large bowel, there are only two mechanisms that drive a laxative effect: large/coarse insoluble fiber particles (eg, wheat bran) mechanically irritate the gut mucosa stimulating water and mucous secretion, and the high water-holding capacity of gel-forming soluble fiber (eg, psyllium) resists dehydration. Both mechanisms require that the fiber resist fermentation and remain relatively intact throughout the large bowel (ie, the fiber must be present in stool), and both mechanisms lead to increased stool water content, resulting in bulky/soft/easy-to-pass stools. Soluble fermentable fibers (eg, inulin, fructooligosaccharide, and wheat dextrin) do not provide a laxative effect, and some fibers can be constipating (eg, wheat dextrin and fine/smooth insoluble wheat bran particles). When making recommendations for a fiber supplement, it is essential to recognize which fibers possess the physical characteristics required to provide a beneficial health effect, and which fiber supplements are supported by reproducible, rigorous evidence of one or more clinically meaningful health benefits