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Multiple sclerosis (MS) is most often diagnosed in women of childbearing age. Therefore, it is important to examine the impact of pregnancy on the course of MS and to enable patients to make decisions about motherhood based on reliable data. The main objective of this study was to assess the impact of pregnancy on the course of MS by comparing the frequency of MS-related hospitalizations during pregnancy and 40 weeks postpartum versus 40 weeks before pregnancy. We used administrative health claims to identify female patients with MS, their deliveries, and their MS-related hospital admissions and calculated the frequency of MS-related hospital admissions before, during, and after pregnancy. We observed that MS is diagnosed approximately three times less often during pregnancy than before or after pregnancy. The number of MS-related hospital admissions decreased during pregnancy, especially in the third trimester. In contrast with other studies, we did not observe an increased level of MS-related admissions postpartum. The number of hospitalizations reported with steroid injections and emergency department visits also decreased during pregnancy. Our results show that pregnancy has a protective effect on the course of MS.

Introduction: The frequency of biologic drug treatment for Polish patients diagnosed with ulcerative colitis (UC) or Crohn disease (CD) has been insufficiently studied., Objectives: We aimed to analyze the use of biologic treatments among Polish patients suffering from inflammatory bowel diseases (IBDs)., Patients and Methods: We used administrative data collected by the National Health Fund (Narodowy Fundusz Zdrowia [NFZ]), Poland's sole public health care payer. IBD cases were defined as cases with at least 2 records assigned code K50 or K51 according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD‑10) and either at least 2 reimbursed prescriptions for IBD drugs or intestinal surgery preceding the record. We identified IBD patients receiving biologic treatments reimbursed by the NFZ in the years 2012-2020. We assessed the percentages of patients receiving biologic treatments in terms of disease type, sex, age group, and place of residence., Results: While 6.8% of Polish CD patients received biologic treatment in 2012, that figure reached 7.9% by 2020. Biologic treatments were given to 0.4% of UC patients in 2014, and 1.6% in 2020. Among patients with both CD and UC, significantly fewer women received biologic therapy than men. The highest percentages of patients receiving biologic treatment for CD and UC were found in the 10-19 age group, while patients over 70 were the adults most rarely treated with biologic drugs., Conclusions: We showed a growing use of biologic agents in the treatment of IBD in Poland. Womenreceive biologic treatment for IBD significantly less frequently than men. The pediatric population features the highest proportion of patients receiving such treatment.

Introduction: The epidemiology of inflammatory bowel disease (IBD) in Poland has been recognized to only a limited extent., Objectives: We aimed to estimate the prevalence and incidence of IBD by analyzing data from the National Health Fund, Poland's sole public health insurer., Patients and Methods: Administrative health claims collected over the 2009-2020 period were used to identify patients with Crohn's disease (CD) or ulcerative colitis (UC). A definition of a case comprised at least 2 records assigned K50 or K51 codes, plus at least 2 prescriptions for IBD drugs reimbursed, or else intestinal surgery preceding the record. The crude and European age‑ standardized rates (EASR) and 95% CIs were calculated for prevalence and incidence. Time trends were also analyzed., Results: As of 2020, there were 23 574 patients with CD and 73 235 with UC. The CD and UC prevalence was respectively 61.6 (EASR 60.3) and 191.4 (EASR 187.85) per 100 000. The prevalence of CD and UC was higher in men (64.1; EASR 61.3 and 201.4; EASR 202.7, respectively) than in women (59.3; EASR 58.4 and 182.0; EASR 175.5, respectively). The incidence of CD was 4.7 per 100 000 (EASR 4.6), and that of UC 12.5 (EASR 12.3). Through the period 2012-2018, the prevalence of both conditions was rising, even though downward trends were noted for the disease incidence., Conclusions: The prevalence and incidence of IBD in Poland are presented, with time trends showing a substantial increase in the disease burden over the years 2009-2020.

Background: The detailed data concerning multiple sclerosis (MS) epidemiology in Poland are based on studies from few and less populated provinces. Therefore, we evaluated MS incidence and prevalence in Poland using electronic administrative health claims (AHCs) from the National Health Fund., Methods: We retrospectively analyzed the AHC financial database collected from 2009 to 2019, encompassing all patients using public health resources. Three different algorithms for identification of MS cases were used: based on studies performed in German population (type 1), tested in the United States (type 2), and one created for the purpose of this study (type 3) that required at least 3 AHCs since 2009 with G35 ICD-10 diagnosis in outpatient specialist care, during hospitalization, and/or at rehabilitation service in any combination within maximally 3 years between the first and the last AHC, and provided that at least one AHC was either in neurological outpatient care or during hospitalization at a neurological ward or prescription of disease-modifying therapy. The American algorithm (type 2) required 3 AHCs within the analyzed year, while the German algorithm (type 1) required only one AHC in the analyzed year., Results: According to the type 3 algorithm, age-adjusted MS incidence and prevalence in 2019 was 6.6 and 131.2 / 100,000 inhabitants, respectively. From 2014 to 2019, the significant trend in increasing prevalence and decreasing incidence of MS was observed (p<0.001). Median age of prevalent MS patients was 50 years (interquartile range, IQR 39-61) whereas median age of incident MS cases was 37 years (IQR 28-48). Female-to-male ratio in MS patients was 2.4. According to the type 1 algorithm, age-adjusted MS incidence and prevalence in 2019 was 11.6 and 244.9 / 100,000 inhabitants, respectively. Use of the type 2 algorithm resulted in estimated age-adjusted MS incidence and prevalence values in 2019 of 6.2 and 120.1 / 100,000 inhabitants, respectively., Conclusions: Multiple sclerosis incidence and prevalence in Poland are higher than previously reported and similar to the numbers shown for central European countries., (Copyright © 2021. Published by Elsevier B.V.)

Immune system function changes during aging, but the molecular mechanisms of this phenomenon are not fully understood. The present study identified pathways that are associated with age-associated changes in human B lymphocytes. Initial in silico analysis of 1355 genes involved in aging revealed the strongest association (p = 4.36E-21) with the gonadotropin-releasing hormone receptor (GnRHR) pathway. Extended analysis of 2736 aging-related genes using updated databases confirmed such association (p = 2.41E-16). Genes involved in both aging and the GnRHR pathway were significantly involved in lymphocyte B and T activation and aging-related phenotypes, including hyperinsulinemia and diabetes, arthritis, cerebrovascular disease, and cancers. We, therefore, examined non-tumorigenic Epstein-Barr virus (EBV)-transformed B-lymphocyte cell lines that originated from 12 young subjects (20-31 years old) and 10 centenarians (100-102 years old). Gonadotropin-releasing hormone I (GnRH-I) and GnRHR levels did not depend on the age of the cell donors. Inhibition of the GnRHR pathway age-independently decreased cell proliferation (p < 0.001) and increased apoptosis (p < 0.001). However, the decrease in immunoglobulin G synthesis (p < 0.01) was twice as high in centenarian cells than in young cells. In conclusion, the GnRHR pathway regulated essential properties of B lymphocytes. However, upon EBV transformation, memory class-switched B cells became the dominant cell subpopulation. Therefore, the observed effects of GnRHR inhibition were attributable to this subpopulation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Increasing evidence supports the observation that multiple sclerosis (MS) has a preclinical period, with various prodromal signs and symptoms more frequently represented in patients with confirmed MS many years later. Considering the apparent gender differences in the incidence and clinical course of MS, it remains unclear whether it could be reflected in prodromal symptom features. This study aimed to compare a broad spectrum of prodromal signs and symptoms between males and females in the 7-year period before the definite diagnosis of MS. Data came from the central register of the national payer of services, financed under the public healthcare system in Poland. They covered a 7-year period of patient health record claims, from 2009 to 2016. The following groups of symptoms were significant with women: musculoskeletal ( p < 0.001), ophthalmic ( p < 0.001), laryngological ( p < 0.001), digestive system ( p < 0.001), urinary tract ( p < 0.001), mental ( p < 0.001), cardiovascular ( p < 0.001), complaints and headaches ( p < 0.001). There was also a weak correlation with head injuries ( p = 0.03) while dermatological and reproductive system complaints did not appear to be significant ( p < 0.05). For males, the following groups of symptoms were significant: musculoskeletal ( p < 0.001), ophthalmic ( p < 0.001), laryngological ( p = 0.007), cardiovascular system symptoms ( p < 0.001), and headaches ( p < 0.001). Interestingly, reproductive system problems were overrepresented in the male population ( p = 0.008). There was no significant correlation with MS risk for dermatological, digestive, urinary, and mental complaints. Similarly, head injuries were not significant. Our results shed more light on well-known differences in the epidemiological and clinical characteristics between sexes in multiple sclerosis, and show differences in prodromal complaints before MS onset.

Objectives: To investigate the influence of overweight and obesity on general performance and mortality in seniors., Design: Cross-sectional multidisciplinary study on ageing of the Polish population., Setting: Community-dwelling individuals aged 65 years or older, selected using three-stage stratified, proportional draw., Participants: 4944 Polish Caucasian seniors, aged 65 years or older recruited between October 2007 and October 2010., Measurements: All study subjects underwent measurement of body mass index (BMI), waist circumference (WC), and arm circumference (AC). The physical and cognitive performance was evaluated using the Katz Activities of Daily Living (ADL) score and Mini-Mental State Examination (MMSE), respectively. Morbidity data were obtained from a medical questionnaire. Mortality data were obtained from the Population Register of Poland between October 2015 and October 2018., Results: Increasing age was associated with a decreased prevalence of obesity (all p<0.001). Higher BMI, WC and AC values were associated with higher ADL and MMSE scores (all p<0.001). On multivariate analysis, all three body measurements in women remained independent predictors of the ADL score (BMI p=0.002, WC p=0.005, AC p<0.001) and MMSE score (p<0.001, p=0.003, p<0.001). In men, physical functioning was associated with AC (p=0.003), and cognitive status was associated with AC (p<0.001) and BMI (p=0.013). There was no association between general obesity, abdominal obesity, or AC with several aging-related adverse conditions. Kaplan-Meier survival curves showed that overweight and obesity were associated with the lowest mortality. On multivariate analysis, BMI and AC values remained independent predictors of mortality. In successfully aging individuals, neither BMI, WC, nor AC remained such predictors., Conclusions: Overweight and obesity in Caucasian seniors are not associated with deterioration of physical and cognitive function or with increased mortality., Competing Interests: The authors have no conflicts of interest to declare

Background: Inflammatory bowel diseases (IBD) often begins early in life. Adolescents and young adults (AYA) with IBD have to acquire behaviors that support self-care, effective healthcare decision-making, and self-advocacy to successfully transition from pediatric to adult health care. Despite the importance of this critical time period, limited empirical study of factors associated with transition readiness in AYA exists. This study aimed to describe transition readiness in a sample of AYA with IBD and identify associated modifiable and nonmodifiable factors., Methods: Seventy-five AYA (ages 16-20) and their parents participated. AYA and parents reported on demographics, patient-provider transition-related communication, and transition readiness. AYA self-reported on disease self-efficacy. Disease information was abstracted from the medical record., Results: Deficits in AYA responsibility were found in knowledge of insurance coverage, scheduling appointments, and ordering medication refills. Older AYA age, higher AYA disease-management self-efficacy, and increased patient-provider transition communication were each associated with higher overall transition readiness and AYA responsibility scores. Regression analyses revealed that older AYA age and increased patient-provider transition-related communication were the most salient predictors of AYA responsibility for disease management and overall transition readiness across parent and AYA reports., Conclusions: AYA with IBD show deficits in responsibility for their disease management that have the potential to affect their self-management skills. Findings suggest provider communication is particularly important in promoting transition readiness. Additionally, it may be beneficial to wait to transition patients until they are older to allow them more time to master skills necessary to responsibly manage their own healthcare.

Background: Although adequate disease-related knowledge is recognized as an important component of transition readiness, little empirical attention has been directed toward understanding the levels of disease knowledge of adolescents and young adults (AYAs) with inflammatory bowel diseases (IBDs) or factors associated with higher levels of knowledge. This study described disease knowledge in a sample of AYAs with IBDs and examined individual, family, and patient-provider relationship factors associated with higher knowledge., Methods: Seventy-five AYAs (ages 16-20) and their parents participated. AYAs and parents reported on demographics, parent autonomy granting behaviors, health care satisfaction, patient-provider transition-related communication, and disease knowledge. AYAs self-reported on disease self-efficacy. Disease information was abstracted from the medical record., Results: On average, AYAs answered 8.20 (SD = 1.75) of 12 knowledge questions correctly. Over 85% of AYAs correctly identified their type of IBD, number and type of IBD-related surgeries, and name of their current IBD medical provider. In contrast, knowledge about frequency of medication refills, effects of drugs and alcohol on IBD, and number to call to schedule medical appointments was suboptimal (i.e., 50% or fewer provided a correct response). Older AYA age, greater AYA health care satisfaction, higher AYA self-efficacy, and more frequent patient-provider transition-related communication were each associated with higher IBD-related knowledge., Conclusions: To promote disease knowledge, providers should foster AYA self-efficacy by encouraging age-appropriate involvement in IBD management and make discussion of transition-related issues a priority during clinical appointments. Moreover, fostering collaborative and positive relationships with patients will improve satisfaction and may also enhance knowledge.

Our recent research on the pineal gland of young chickens confirmed that three genes encoding enzymes involved in pineal melatonin biosynthesis, tryptophan hydroxylase 1 (Tph1), arylalkylamine-N-acetyltransferase (Aanat) and acetylserotonin O-methyltransferase (Asmt), are transcribed rhythmically under light:dark (L:D) 12:12 conditions in vivo. Additionally, in the pineal gland of maturing chickens, the dopa decarboxylase (Ddc) gene is transcribed rhythmically at a specific stage of the developmental process. Therefore, the aim of the present study was to verify whether all of these genes are transcribed rhythmically in vivo under constant darkness (D:D) and in pinealocyte cultures under both L:D and D:D. Experiments were performed on chickens maintained under L:D 12:12 conditions. Chickens at 15 days of age were divided into two groups; chickens from the first group remained under the same conditions, whereas those from the second group were kept in darkness. Subsequently, 16-day-old animals were sacrificed every 2 hours over a 24-h period. For the in vitro experiments, 16-day-old chickens were sacrificed at ZT 6, and their pineal glands were isolated. Pineal cultures were maintained for up to two days in L:D conditions. Then, the pinealocyte cultures were divided into two groups: the first remained under L:D conditions, whereas the second was transferred to D:D conditions. Pinealocytes were subsequently collected every 2 hours over a 24-h period. Transcription was evaluated using the RT-qPCR method, and the rhythm percentage was calculated through Cosinor analysis. The mRNA levels of all genes examined were rhythmic under all conditions. Moreover, in silico analysis of the promoters of all of the genes examined revealed the presence of enhancer box sequences in all of the promoters as well as DBP/E4BP4 binding elements in the promoters of Tph1 and Asmt. This suggests that these genes may all be regulated transcriptionally by the molecular clock mechanism and may be considered clock as controlled genes.

MicroRNAs (miRNAs) are small non-coding RNAs that participate in the regulation of gene expression. Their role during mammary gland development is still largely unknown. In this study, we performed a microarray analysis to identify miRNAs associated with high mammogenic potential of the bovine mammary gland. We identified 54 significantly differentially expressed miRNAs between the mammary tissue of dairy (Holstein-Friesian, HF) and beef (Limousin, LM) postpubertal heifers. Fifty-two miRNAs had higher expression in the mammary tissue of LM heifers. The expression of the top candidate miRNAs (bta-miR-10b, bta-miR-29b, bta-miR-101, bta-miR-375, bta-miR-2285t, bta-miR-146b, bta-let7b, bta-miR-107, bta-miR-1434-3p) identified in the microarray experiment was additionally evaluated by qPCR. Enrichment analyses for targeted genes revealed that the major differences between miRNA expression in the mammary gland of HF versus LM were associated with the regulation of signalling pathways that are crucial for mammary gland development, such as TGF-beta, insulin, WNT and inflammatory pathways. Moreover, a number of genes potentially targeted by significantly differentially expressed miRNAs were associated with the activity of mammary stem cells. These data indicate that the high developmental potential of the mammary gland in dairy cattle, leading to high milk productivity, depends also on a specific miRNA expression pattern., (© 2015 Blackwell Verlag GmbH.)

Background: A gap exists in the literature on celiac disease populations and the response to hepatitis B vaccination., Objective: To identify pediatric patients with celiac disease who received the primary hepatitis B vaccination and investigate their response to vaccine., Design/methods: Patients underwent blood draw for hepatitis B surface antibody titers. Patients with undetectable or non-protective HBsAb titers were contacted. Study outcome measures and patient characteristics variables were summarized by means, standard deviations, medians, and ranges. A two-sample t-test was used to compare normally distributed continuous variables between responders and non-responders., Results: In all, 58% of patients did not meet the threshold for "protective" antibody titers. The mean time between completion of hepatitis B vaccination and diagnosis of celiac disease was 8.1 years for responders versus 10.5 years for non-responders. In a multivariate analysis, time between completion of vaccine and diagnosis of celiac disease was statistically significant predictor of response with an adjusted odds ratio of 0.69 (95% confidence interval: 0.50-0.95; p = 0.021)., Conclusion: Our celiac disease population shows a high hepatitis B vaccine failure. The time between completion of vaccine series and diagnosis of celiac disease is an independent predictor for response.

Background: Epidemiological studies of pediatric inflammatory bowel diseases (IBD) are needed to generate etiological hypotheses and inform public policy; yet, rigorous population-based studies of the incidence and natural history of Crohn's disease (CD) and ulcerative colitis (UC) in the United States are limited., Methods: We developed a field-tested prospective system for identifying all new cases of IBD among Wisconsin children over an 8-year period (2000-2007). Subsequently, at the end of the study period, we retrospectively reconfirmed each case and characterized the clinical course of this incident cohort., Results: The annual incidence of IBD among Wisconsin children was 9.5 per 100,000 (6.6 per 100,000 for CD and 2.4 per 100,000 for UC). Approximately 19% of incident cases occurred in the first decade of life. Over the 8-year study period, the incidence of both CD and UC remained relatively stable. Additionally, (1) childhood IBD affected all racial groups equally, (2) over a follow-up of 4 years, 17% of patients with CD and 13% of patients with patients with UC required surgery, and (3) 85% and 40% of children with CD were treated with immunosuppressives and biologics, respectively, compared with 62% and 30% of patients with UC., Conclusions: As in other North American populations, these data confirm a high incidence of pediatric-onset IBD. Importantly, in this Midwestern U.S. population, the incidence of CD and UC seems to be relatively stable over the last decade. The proportions of children requiring surgery and undergoing treatment with immunosuppressive and biological medications underscore the burden of these conditions.

Unlabelled: There is significant variation in diagnostic testing and treatment for inflammatory bowel disease. Quality improvement science methods can help address unwarranted variations in care and outcomes., Methods: The ImproveCareNow Network was established under the sponsorship of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the American Board of Pediatrics as a prototype for a model of improving subspecialty care that included three components: 1) creating enduring multicenter collaborative networks of pediatric subspecialists, 2) sharing of performance data collected in patient registries, and 3) training in quality improvement. The network began with a focus on improving initial diagnostic testing and evaluation, the classification of the severity and extent of disease, the detection and treatment of inadequate nutrition and growth, and the appropriate dosing of immunomodulator medications. Changes are based on an evidence-based model of chronic illness care involving the use of patient registries for population management, previsit planning, decision support, promoting self-management, and auditing of care processes., Results: Currently, patients are being enrolled at 23 sites. Through 2009, data have been analyzed on over 2500 patients from over 7500 visits. Initial results suggest improvements in both care processes (e.g., appropriate medication dosing and completion of a classification bundle that includes the patient's diagnosis, disease activity, distribution and phenotype, growth status, and nutrition status) and outcomes (e.g., the percentage of patients in remission)., Conclusions: These improvements suggest that practice sites are learning how to apply quality improvement methods to improve the care of patients., (Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.)

Background: Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker to determine the degree of intestinal inflammation and predicting relapse in patients with inflammatory bowel disease (IBD). The aim was to compare FC levels in IBD and healthy controls, to correlate FC levels with clinical disease activity, and to assess whether FC levels can be used to predict clinical relapse in children with IBD., Methods: Enzyme-linked immunosorbent assay (ELISA) determined levels of FC were measured in more than 1 stool samples (n) from 32 IBD patients (n = 97) and from 34 healthy controls (n = 37). Disease activity was assessed by the Harvey-Bradshaw index in Crohn's disease (CD) and by Physician's Global Assessment (PGA) in both CD and ulcerative colitis (UC). Clinical events were recorded up to 9 months following stool collection in CD patients. Wilcoxon rank sum test and Fisher's exact tests were used to compare FC levels in IBD patients and in control. Kaplan-Meyer analysis was used to determine a risk of clinical relapse in relation to FC levels., Results: The IBD group had higher FC levels (range 17-7500 g/g) compared with control (16-750 g/g, P < 0.0001). FC levels were higher during relapse (CD, 3214 +/- 2186; UC, 2819 +/- 1610) compared to remission (CD, 1373 +/- 1630; UC, 764 +/- 869; P < 0.0001). Among those with clinical relapse, 90% had FC levels more than 400 mug/g in CD. Eighty-nine percent of CD encounters with FC levels less than 400 mug/g remained in clinical remission., Conclusions: FC levels differentiate active IBD from controls. Among children with CD and in remission, FC levels may be useful in predicting impending clinical relapse.