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Fifteen Years of Iodine Prophylaxis in Italy: Results of a Nationwide Surveillance (Period 2015-2019).
De Angelis, S, Medda, E, Rotondi, D, Masocco, M, Minardi, V, Contoli, B, Possenti, V, Sorbo, A, D'Amato, M, Turco, AC, et al
The Journal of clinical endocrinology and metabolism. 2024;(2):e495-e507
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Abstract
CONTEXT In 2005, a nationwide program of iodine prophylaxis on a voluntary basis was implemented in Italy by law. However, recent data on iodine status are lacking. OBJECTIVE The aim of this study was to evaluate efficiency, effectiveness, and possible adverse effects (increased occurrence of thyroid autoimmunity and hyperthyroidism) of the Italian iodine prophylaxis program. METHODS From 2015 to 2019, a nationwide survey was performed. The use of iodized salt was evaluated in a sample of 164 593 adults and in 998 school canteens. A sample of 4233 schoolchildren (aged 11-13 years) was recruited to assess urinary iodine concentration, prevalence of goiter, and thyroid hypoechogenicity on ultrasound, with the latter being an indirect indicator of thyroid autoimmunity. Neonatal TSH values of 197 677 infants screened in regions representative of Northern, Central, and Southern Italy were analyzed to investigate the percentage of TSH values >5.0 mIU/L. Data on methimazole prescriptions were analyzed as indirect indicators of new cases of hyperthyroidism. RESULTS The prevalence of the use of iodized salt was 71.5% in adult population and 78% in school canteens. A median urinary iodine concentration of 124 μg/L, a prevalence of goiter of 2.2%, and a prevalence of thyroid hypoechogenicity of 5.7% were observed in schoolchildren. The percentage of neonatal TSH values >5.0 mIU/L resulted still higher (5.1%) than the World Health Organization threshold of 3.0%, whereas the prescriptions of methimazole showed a reduction of 13.5%. CONCLUSION Fifteen years of iodine prophylaxis have led to iodine sufficiency in Italy, although there still is concern about iodine nutritional status during pregnancy.
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Human Leukocyte Antigen Signatures as Pathophysiological Discriminants of Microscopic Colitis Subtypes.
Zheng, T, Roda, G, Zabana, Y, Escudero-Hernández, C, Liu, X, Chen, Y, Camargo Tavares, L, Bonfiglio, F, Mellander, MR, Janczewska, I, et al
Journal of Crohn's & colitis. 2024;(3):349-359
Abstract
BACKGROUND AND AIMS Microscopic colitis [MC] is currently regarded as an inflammatory bowel disease that manifests as two subtypes: collagenous colitis [CC] and lymphocytic colitis [LC]. Whether these represent a clinical continuum or distinct entities is, however, an open question. Genetic investigations may contribute important insight into their respective pathophysiologies. METHODS We conducted a genome-wide association study [GWAS] meta-analysis in 1498 CC, 373 LC patients, and 13 487 controls from Europe and the USA, combined with publicly available MC GWAS data from UK Biobank and FinnGen [2599 MC cases and 552 343 controls in total]. Human leukocyte antigen [HLA] alleles and polymorphic residues were imputed and tested for association, including conditional analyses for the identification of key causative variants and residues. Genetic correlations with other traits and diagnoses were also studied. RESULTS We detected strong HLA association with CC, and conditional analyses highlighted the DRB1*03:01 allele and its residues Y26, N77, and R74 as key to this association (best p = 1.4 × 10-23, odds ratio [OR] = 1.96). Nominally significant genetic correlations were detected between CC and pneumonia [rg = 0.77; p = 0.048] and oesophageal diseases [rg = 0.45, p = 0.023]. An additional locus was identified in MC GWAS analyses near the CLEC16A and RMI2 genes on chromosome 16 [rs35099084, p = 2.0 × 10-8, OR = 1.31]. No significant association was detected for LC. CONCLUSION Our results suggest CC and LC have distinct pathophysiological underpinnings, characterised by an HLA predisposing role only in CC. This challenges existing classifications, eventually calling for a re-evaluation of the utility of MC umbrella definitions.
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Observational pilot study: A comparison of amino acids and derangement of intestinal function between healthy ageing subjects and patients affected by chronic kidney disease stage CKD3b-4 in conservative management.
Bolasco, P, Aquilani, R, Maestri, R, Esposito, MP, Deiana, ML, Cadeddu, M, Secci, R, Casu, B, Serra, A, Iadarola, P, et al
Clinical nutrition ESPEN. 2023;:10-19
Abstract
BACKGROUND AND AIMS A comparison of the amino acid (AA) plasma profile and markers of intestinal absorption-inflammation between healthy subjects aged 65-70 years and age-matched patients affected by stage 3b-4 chronic kidney disease (CKD3b-4) was performed. METHODS Eleven healthy volunteers were compared with 12 CKD3b-4 patients at their first outpatient control (T0) and after 12-months (T12). Adherence to a low protein diet (LPD, 0.6 ± 0.1 g/kg/day) was assessed by Urea Nitrogen Appearance. The following parameters were assessed: renal function, nutritional parameters, bioelectrical impedance analysis, plasma levels of 20 total amino acids (TAAs), both essential (EAAs) including branched-chain amino acids (BCAAs) and non-essential (NEAAs). Zonulin and faecal Calprotectin markers were used to evaluate intestinal permeability/inflammation. RESULTS Four patients dropped out of the study; in the remaining 8 residual kidney function (RKF) remained stable, their LPD adherence had risen to 0.89 g/kg/day, anaemia had worsened and extracellular body fluid had increased. In comparison to healthy subjects, TAA levels of histidine, arginine, asparagine, threonine, glycine, and glutamine had all increased. No variation in BCAAs was observed. A significant increase was detected in faecal calprotectin and zonulin levels in CKD patients as the disease progressed. CONCLUSIONS This study confirms the finding in aged patients of an alteration in plasmatic levels of several AAs secondary to uraemia. Intestinal markers provide confirmation of a relevant alteration to the intestinal function in CKD patients.
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Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations.
Thomas, M, Su, YR, Rosenthal, EA, Sakoda, LC, Schmit, SL, Timofeeva, MN, Chen, Z, Fernandez-Rozadilla, C, Law, PJ, Murphy, N, et al
Nature communications. 2023;(1):6147
Abstract
Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
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A Starch- and Sucrose-Reduced Diet in Irritable Bowel Syndrome Leads to Lower Circulating Levels of PAI-1 and Visfatin: A Randomized Controlled Study.
Roth, B, Myllyvainio, J, D'Amato, M, Larsson, E, Ohlsson, B
Nutrients. 2022;(9)
Abstract
Irritable bowel syndrome (IBS) is characterized by gastrointestinal symptoms. Overweight and increased risk of metabolic syndromes/diabetes are observed in IBS, conditions associated with plasminogen activator inhibitor-1 (PAI-1) and visfatin. The aim of this study was to measure blood levels of AXIN1, cholecystokinin (CCK), enkephalin, ghrelin, neuropeptide Y (NPY), PAI-1, and visfatin before and after a 4-week intervention with a starch- and sucrose-reduced diet (SSRD). A total of 105 IBS patients were randomized to either SSRD (n = 80) or ordinary diet (n = 25). Questionnaires were completed, and blood was analyzed for AXIN1 and hormones. AXIN1 (p = 0.001) and active ghrelin levels (p = 0.025) were lower in IBS than in healthy volunteers at baseline, whereas CCK and enkephalin levels were higher (p < 0.001). In the intervention group, total IBS-symptom severity score (IBS-SSS), specific gastrointestinal symptoms, psychological well-being, and the influence of intestinal symptoms on daily life were improved during the study, and weight decreased (p < 0.001 for all), whereas only constipation (p = 0.045) and bloating (p = 0.001) were improved in the control group. PAI-1 levels tended to be decreased in the intervention group (p = 0.066), with a difference in the decrease between groups (p = 0.022). Visfatin levels were decreased in the intervention group (p = 0.007). There were few correlations between hormonal levels and symptoms. Thus, this diet not only improves IBS symptoms but also seems to have a general health-promoting effect.
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Detailed stratified GWAS analysis for severe COVID-19 in four European populations.
Degenhardt, F, Ellinghaus, D, Juzenas, S, Lerga-Jaso, J, Wendorff, M, Maya-Miles, D, Uellendahl-Werth, F, ElAbd, H, Rühlemann, MC, Arora, J, et al
Human molecular genetics. 2022;(23):3945-3966
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Abstract
Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
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Effects of a Novel Amino Acid Formula on Nutritional and Metabolic Status, Anemia and Myocardial Function in Thrice-Weekly Hemodialysis Patients: Results of a Six-Month Randomized Double-Blind Placebo-Controlled Pilot Study.
Murtas, S, Aquilani, R, Fiori, G, Maestri, R, Iadarola, P, Graccione, C, Contu, R, Deiana, ML, Macis, F, Secci, R, et al
Nutrients. 2022;(17)
Abstract
(1) Background: Chronic Kidney Disease (CKD) induces metabolic derangement of amino acid (AA) kinetics, eliciting severe damage to the protein anabolism. This damage is further intensified by a significant loss of AAs through hemodialysis (HD), affecting all tissues with a high metabolic turnover, such as the myocardium and body muscle mass. (2) Aim: to illustrate the effects of a novel AA mixture in boosting mitochondrial energy production. (3) Methods: A strict selection of 164 dialysis patients was carried out, allowing us to finally identify 22 compliant patients who had not used any form of supplements over the previous year. The study design envisaged a 6-month randomized, double-blind trial for the comparison of two groups of hemodialysis patients: eleven patients (67.2 ± 9.5 years) received the novel AA mix (TRG), whilst the other eleven (68.2 ± 10.5 years) were given a placebo mix that was indistinguishable from the treatment mix (PLG). (4) Results: Despite the 6-month observation period, the following were observed: maintenance of target hemoglobin values with a reduced need for erythropoiesis-stimulating agents in TRG > 36% compared to PLG (p < 0.02), improved phase angle (PhA) accompanied by an increase in muscle mass solely in the TRG group (p < 0.05), improved Left Ventricular Ejection Fraction (LVEF > 67%) in the TRG versus PLG group (p < 0.05) with early but marked signs of improved diastolic function. Increased sensitivity to insulin with greater control of glycemic levels in TRG versus PLG (p = 0.016). (5) Conclusions: the new AA mix seemed to be effective, showing a positive result on nutritional metabolism and cardiac performance, stable hemoglobin levels with the need for lower doses of erythropoietin (EPO), insulin increased cell sensitivity, better muscle metabolism with less loss of mass.
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Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study.
Berens, S, Dong, Y, Fritz, N, Walstab, J, D'Amato, M, Zheng, T, Wahl, V, Boekstegers, F, Bermejo, JL, Martinez, C, et al
World journal of gastroenterology. 2022;(21):2334-2349
Abstract
BACKGROUND Single-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (HTR3) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations exist in irritable bowel syndrome (IBS). AIM: To assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS. METHODS In this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs - HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A - were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays. RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model (F depressive = 7.475, P depressive = 0.006; F anxiety = 6.535, P anxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score (F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT3AC variant receptors. CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.
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A starch- and sucrose-reduced dietary intervention in irritable bowel syndrome patients produced a shift in gut microbiota composition along with changes in phylum, genus, and amplicon sequence variant abundances, without affecting the micro-RNA levels.
Nilholm, C, Manoharan, L, Roth, B, D'Amato, M, Ohlsson, B
United European gastroenterology journal. 2022;(4):363-375
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Abstract
BACKGROUND/AIM: A randomized clinical trial with a starch- and sucrose-reduced diet (SSRD) in irritable bowel syndrome (IBS) patients has shown clear improvement of participants' symptoms. The present study aimed to explore the effects of the SSRD on the gut microbiota and circulating micro-RNA in relation to nutrient intake and gastrointestinal symptoms. METHODS IBS patients were randomized to a 4-week SSRD intervention (n = 80) or control group (n = 25); habitual diet). At baseline and 4 weeks, blood and fecal samples, 4 day-dietary records, and symptom questionnaires were collected, that is, Rome IV questionnaires, IBS-symptom severity score (IBS-SSS) and visual analog scale for IBS (VAS-IBS). Micro-RNA was analyzed in blood and microbiota in faeces by 16S rRNA from regions V1-V2. RESULTS The alpha diversity was unaffected, whereas beta diversity was decreased (p < 0.001) along with increased abundance of Proteobacteria (p = 0.0036) and decreased abundance of Bacteroidetes phyla (p < 0.001) in the intervention group at 4 weeks. Few changes were noted in the controls. The shift in beta diversity and phyla abundance correlated with decreased intakes of carbohydrates, disaccharides, and starch and increased fat and protein intakes. Proteobacteria abundance also correlated positively (R2 = 0.07, p = 0.0016), and Bacteroidetes negatively (R2 = 0.07, p = 0.0017), with reduced total IBS-SSS. Specific genera, for example, Eubacterium eligens, Lachnospiraceae UCG-001, Victivallis, and Lachnospira increased significantly in the intervention group (p < 0.001 for all), whereas Marvinbryantia, DTU089 (Ruminoccocaceae family), Enterorhabdus, and Olsenella decreased, together with changes in amplicon sequence variant (ASV) levels. Modest changes of genus and ASV abundance were observed in the control group. No changes were observed in micro-RNA expression in either group. CONCLUSION The SSRD induced a shift in beta diversity along with several bacteria at different levels, associated with changes in nutrient intakes and reduced gastrointestinal symptoms. No corresponding changes were observed in the control group. Neither the nutrient intake nor the microbiota changes affected micro-RNA expression. The study was registered at ClinicalTrials.gov data base (NCT03306381).
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Microscopic colitis.
Burke, KE, D'Amato, M, Ng, SC, Pardi, DS, Ludvigsson, JF, Khalili, H
Nature reviews. Disease primers. 2021;(1):39
Abstract
Microscopic colitis (MC) is an inflammatory disease of the large intestine associated with urgent watery diarrhoea. MC may occur in people of all ages, although the disease primarily affects older women. Once believed to be rare, MC is now known to be a common cause of chronic watery diarrhoea in high-income countries, affecting 1 in 115 women and 1 in 286 men during their lifetime in Swedish population-based estimates. An inappropriate immune response to disturbances in the gut microenvironment is implicated in the pathogenesis of MC. Evidence also supports an underlying genetic basis for disease. The diagnosis of MC relies on clinical symptoms and microscopic assessment of colonic biopsy samples. MC is categorized histologically into collagenous colitis, lymphocytic colitis and their incomplete forms. The mainstay of treatment includes the use of budesonide, with or without adjunctive therapies, and withdrawal of offending drugs. Emerging studies suggest a role for biologicals and immunosuppressive therapies for the management of budesonide-refractory or budesonide-dependent disease. MC can have a substantial negative effect on patient quality of life. The outlook for MC includes a better understanding of the immune response, genetics and the microbiome in disease pathogenesis along with progress in disease management through robust clinical trials.