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Background The prevalence of atopic dermatitis (AD) has increased, but studies in adult or elderly populations are sparse. Methods We investigated 12-month and lifetime prevalences of AD in the Finnish adult population ≥30 years of age and analyzed living environment factors, socioeconomic factors, lifestyle-related factors, and serum vitamin D levels for their associations with AD in a national health examination survey. Results The lifetime prevalence was 21.9% and 12-month prevalence 10.1%. The highest prevalence (lifetime 28.6%, 12-month 15.4%) was seen in subjects 30-39 years of age. Prevalence decreased with age. Subjects with highly educated parents were more likely to have active AD, though there was no effect of higher education in subjects themselves. Younger age and being an ex-smoker were associated with active AD. Female sex and daily smoking increased the risk in subjects 30-49 years of age. There was no dose– response relationship to serum vitamin D levels and no association with the living environment. Conclusions Our data show that the number of adult patients with atopic dermatitis has grown and prevalence numbers of AD in Finnish adults are among the highest reported. Together with the aging of the society, the burden of AD is not limited to childhood.

BACKGROUND: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. OBJECTIVE: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. METHOD: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8–20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. RESULTS: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with

Serum alpha-klotho (s-klotho) protein has been linked with lifespan, and low concentrations of s-klotho have been associated with worse physical and cognitive outcomes. Although its significance in aging remains unclear, s-klotho has been proposed as a molecular biomarker of frailty and dependence. This study is a secondary analysis of data from a clinical trial performed in a population of 103 older individuals living in 10 nursing homes in Gipuzkoa (Spain). We aimed to elucidate associations between s-klotho (as measured by enzyme-linked immunosorbent assay) and body composition, physical fitness, and cognition, as well as frailty and dependence (determined using validated tests and scales). In addition, we investigated the association of s-klotho concentration with falls in the six months following the initial assessment. Low s-klotho levels were associated with a lower score in the psychological component of the Tilburg Frailty Indicator, a worse score in the Coding Wechsler Adult Intelligence Scale, and a greater dependence in activities of daily living. Moreover, participants with lower s-klotho concentrations suffered more falls during the 6 months after the assessment. Future translational research should aim to validate klotho's putative role as a biomarker that could identify the risk of aging-related adverse events in clinical practice. This work was supported by grants from the Basque government (ELKARTEK15/39, ELKARTEK16/57, ELKARTEK17/61, RIS16/07, SAN17/11), the Euskampus Fundazioa Foundation, and the Convention between UPV/EHU and the Gipuzkoa Provincial Council (Gipuzkoa Eraikiz). Haritz Arrieta and Chloe Rezola were supported by two fellowships from the University of the Basque Country (UPV/EHU)

Objective: Hashimoto's thyroiditis (HT) is a variant of autoimmune thyroid disorders (AITD) which has been associated with vitamin D (vit-D) deficiency. However, whether vit-D supplementation is linked to reduction of thyroid autoantibodies and improvement of thyroid function is not well characterized. The present study was planned to evaluate the effect of vit-D supplementation on possible improvement of thyroid auto antibody titer and thyroid hormone profile in patients with AITD subjects.Methods:Twenty-three patients of HT were given weekly supplementation of 60,000 IU vit-D for 8 weeks followed by once a month for another 4 months. After 6 months of vit-D supplementation, thyroid autoantibody titer (TPO antibody) and thyroid hormone profile was rechecked.Results: Mean serum vit-D was increased significantly from 15.33 ± 5.71 to 41.22 ± 12.24 ng/mL (normal levels) after supplementation. There was significant increase in thyroid autoantibody titre (from 746.8 ± 332.2 to 954.1 ±4 59.8 IU/ml; P= 0.006) and TSH level (7.23 ± 3.16 to 3.04 ± 2.62 (mIU/L);P = 0.01) following 6 months of vit-D supplementation. Conclusion: Vitamin-D levels were low in AITD patients in eastern India and, its supplementation in HT patients increased thyroid antibody titer and there was significant reduction in serum TSH and increased in free T4.

Background: Acute Otitis media (AOM) and its recurrence is a prevalent health problem among pre-school children. Different strategies to prevent recurrent have been established with questionable efficacy. Vitamin D is suspected as a possible preventable risk factor. Aim of the work:To evaluate the effect of vitamin-D supplementation on recurrence rate of acute otitis media among Pre-school children. Patients and Methods:60 pre-school children with a recurrent episode of acute otitis media [by history and otoscopic examination] were included. After diagnosis, all children received standard treatment and after recovery, serum levels of vitamin-D were estimated; those with reduced vitamin D had been included, then divided into: Study group (30 children, received oral vitamin-D supplementation for 4 months; and Control group (30 children; received placebo). New attacks of AOM had been document during the regular visits for the six months. Vitamin D had been re-estimated after 6 months. Results: Both groups were comparable regarding studied variables at the start. Upper respiratory tract infection and ear discharge significantly decreased; vitamin D significantly increased among study group at 6 months. Recurrent AOM after 6 months, had been significantly reduced among study vs control group (1.43±0.62 vs 3.46±0.62 respectively). Also, vitamin-D significantly increased at the end in study vs control group (21.76±5.95 vs 14.53±4.73 ng/ml respectively). The mean percentage of increase of vitamin-D in study group was 135.98% compared to 33.91%. In control group. Conclusion: Vitamin D supplementation to children with a history of rAOM plays a significant role in reduction of attack frequency.

Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure. Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability. Results: The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality. Conclusions: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.

Introduction: Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are leading causes of morbidity and mortality for both mother and fetus. It has been proposed that vitamin D affects a number of biological processes involved in the pathogenesis of hypertensive disorders of pregnancy. Therefore, a seasonal variation in the risk of these disorders might be expected in areas such as Denmark with marked seasonal variation in sunlight exposure. In this study, we aimed to evaluate the existence of this association. Material and methods: We used information from a cohort of 50 665 previously healthy, nulliparous women with singleton pregnancies. All women gave birth between 1989 and 2010 at Aarhus University Hospital, Denmark. Logistic regression analyses combined with the cubic spline method were used to estimate the seasonal variation for each outcome: gestational hypertension and preeclampsia, after adjusting for calendar time. Results: Of the 50 665 women included, 8.5% were diagnosed with a hypertensive disorder of pregnancy. The overall tendency was towards increasing risk when conceiving during spring and early summer, peaking midsummer, and subsequently decreasing steadily during late summer and fall to reach the nadir by winter. Seasonal variation was found for; gestational hypertension (P =.01); preeclampsia (P =.001) and early-onset preeclampsia (P =.014). Conclusions: We found a seasonal variation in the risk of the hypertensive disorders of pregnancy in a large cohort of Danish nulliparous women. The highest risk was seen in women with the estimated date of conception in June and August, that is, during summer. Seasonal variation in vitamin D status may explain this association.

Purpose Adequate calcium intake during pregnancy is of major importance for the health of both mother and fetus. Up to date, evidence on the prevalence of inadequate calcium intake among pregnant women is sparse for Western countries, and it is unknown to what extent inadequate dietary calcium intake is adequately balanced by supplement use. The objective of this study was to estimate calcium intake from diet and supplement use during the early pregnancy in The Netherlands. Methods As part of the Expect cohort study, 2477 pregnant women (8-16 weeks of gestation) completed an online questionnaire including questions on baseline characteristics, the use of calcium containing supplements, and a short food-frequency questionnaire (FFQ). Intake data were used to calculate median calcium intakes from diet, from supplements, and combined, and to compare these values with currently accepted requirement levels. Results Forty-two percent of the pregnant women had a total calcium intake below the estimated average requirement of 800 mg/day. Median (interquartile range) calcium intake was 886 (611-1213) mg/day. Calcium or multivitamin supplements were used by 64.8% of the women at 8 weeks of gestation, with a median calcium content of 120.0 (60.0-200.0) mg/day. Prenatal vitamins were the most often used supplements (60.6%). Conclusions Forty-two percent of Dutch pregnant women have an inadequate calcium intake. Supplements are frequently used, but most do not contain sufficient amounts to correct this inadequate intake.

Background: Bronchial asthma Affecting 1-18% of children in different countries, it widely distributed chronic respiratory disease. vitamin-D increase calcium absorption from the gastrointestinal tract, determines bone health and regulates neuromuscular function. In addition, vitamin-D is a potent immune system regulator, and it has a potential role in various allergic diseases. Aim of the work: To estimate the association between asthma and Vitamin-D in pediatrics. Patients and methods: The present work is a case control study included 150 (100 asthmatic children and 50 healthy control) children aged between 5 and 12 years. Serum 25- hydroxy vitamin-D levels were evaluated and compared between two groups. Association between vitamin-D and pulmonary function was studied in asthmatic children. Results: Cases had significantly lower values of FEV1%, FEV1/FVC ratio and vitamin-D levels when compared to controls (53.20±6.27, 68.64±4.42, 24.44±20.92 vs 126.44±10.15, 107.20±5.05 and 84.25±41.79 successively). In addition, vitamin-D was positively and significantly correlated with pulmonary function tests (FEV1% and FEV1/FVC ratio). Conclusion: Children with bronchial asthma suffered from marked reduction of vitamin-D which correlated with asthma severity.

Objectives: To perform a correlation analysis of serum 25-hydroxy Vitamin-D[25-OH-D], bone turnover markers (BTMs), and bone mineral density (BMD) in patients with gestational diabetes mellitus (GDM) during mid- and late pregnancy and state the significance of these factors for guiding clinical prevention and control of GDM. Methods: This study involved 100 pregnant women with singleton pregnancies who visited our obstetrics and gynecology department, Baoding First Central Hospital, during January 2019 and December 2020. All participants had received more than five prenatal checkups and were assigned to a GDM group and a normal group according to the presence of GDM during the mid-pregnancy period. Serum 25-OH-D, BMD, and bone turnover markers (BTMs) were measured to analyze the differences between the two groups and observe possible correlations among these factors. Results: According to the examination results, GDM occurred in 31 (31%) participants, and the rest 69 (69%) were free of GDM during mid-pregnancy. No significant differences were observed between the two groups in basic clinical data and the serum levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) (p>0.05), whereas the fasting blood glucose (FBG) level in the GDM group was significantly higher than in the normal group (p

Context Phosphate homeostasis and its modifiers in early childhood are inadequately characterized. Objective To determine physiological plasma phosphate concentration and modifying factors in healthy infants at 12 to 24 months of age. Design This study included 525 healthy infants (53% girls), who participated in a randomized vitamin D intervention trial and received daily vitamin D3 supplementation of either 10 or 30 μg from age 2 weeks to 24 months. Biochemical parameters were measured at 12 and 24 months. Dietary phosphate intake was determined at 12 months. Main Outcome Measures Plasma phosphate concentrations at 12 and 24 months of age. Results Mean (SD) phosphate concentration decreased from 12 months (1.9 ± 0.15 mmol/L) to 24 months (1.6 ± 0.17 mmol/L) of age (P 0.472 for all). Plasma iron was associated positively with plasma phosphate at both time points (B, 0.006 and 0.005; 95% CI, 0.004-0.009 and 0.002-0.008; P Conclusion Plasma phosphate concentration decreased from age 12 to 24 months. In infants and toddlers, the strongest plasma phosphate modifiers were sex, iron, and creatinine, whereas vitamin D supplementation did not modify phosphate concentrations.

The development, progression, diagnosis and treatment of autoimmune diseases, such as multiple sclerosis (MS), are convoluted processes which remain incompletely understood. Multiple studies demonstrated that the interleukin (IL)-2 – IL-2 receptor (IL-2R) pathway plays a pivotal role within these processes. The most striking functions of the IL-2 – IL-2R pathway are the differential induction of autoimmune responses and tolerance. This paradoxical function of the IL-2 – IL-2R pathway may be an attractive therapeutic target for autoimmune diseases such as MS. However, the exact mechanisms that lead to autoimmunity or tolerance remain to be elucidated. Furthermore, another factor of this pathway, the soluble form of the IL-2R (sIL-2R), further complicates understanding the role of the IL-2 – IL-2R pathway in MS. The challenge is to unravel these mechanisms to prevent, diagnose and recover MS. In this review, first, the current knowledge of MS and the IL-2 – IL-2R pathway are summarized. Second, the key findings of the relation between the IL-2 – IL-2R pathway and MS have been highlighted. Eventually, this review may launch broad interest in the IL-2 – IL-2R pathway propelling further research in autoimmune diseases, including MS., Highlights • The IL-2 – IL-2R pathway determines the balance between immunity and tolerance. • The IL-2 – IL-2R pathway is involved in the pathogenesis of multiple sclerosis. • The role of soluble IL-2R is controversial and requires further investigation.

SUMMARY: This study analyzed the effect of sodium bisulfate (SBS) supplementation on performance, intestinal morphology, and vitamin D3 status of broilers subjected to a 2X dose coccidiosis vaccine. Coccidiosis causes detrimental effects to poultry health and substantial economic losses to the poultry industry worldwide. At day of placement, 800 one-day-old male Cobb500 broiler chicks were randomly assigned to a vaccinated or not vaccinated group for each of the 2 dietary treatments, control or SBS. Broilers were placed in floor pens for a 21-day trial period. SBS was supplemented at 0.4% at the expense of sodium chloride. Replicates were arranged in a completely randomized block design with 25 broilers per replicate and 8 replicates per treatment, a 2 × 2 factorial arrangement. Body weights (BW), feed consumption (FC), and mortality-corrected feed conversion (FCR) were calculated at day 7, 14, and 21. Serum concentration of 25-hydroxycholecalciferol (25-OH-D3), villi and crypt measurements from small intestine, and tibia ash (TBA) were measured on day 10, and 21 along with lesion scores. Lesion scores were significantly higher (P < 0.05) for vaccinated groups compared to not vaccinated groups, suggestive of a good vaccine challenge. At day 21 there was a significant improvement (P < 0.05) in 25-OH-D3 serum concentration, BW, FCR, and 10 d TBA from SBS compared to Control. In conclusion, the data suggest that SBS can positively impact cumulative FCR, 25-OH-D3 serum concentration, and TBA in broilers.

We describe the profile of dietary supplement use and its correlates in the Epirus Health Study cohort, which consists of 1237 adults (60.5% women) residing in urban north-west Greece. The association between dietary supplement use and demographic characteristics, lifestyle behaviors, personal medical history and clinical measurements was assessed using logistic regression models, separately for women and men. The overall prevalence of dietary supplement use was 31.4%, and it was higher in women (37.3%) compared to men (22.4%, p-value = 4.2−08). Based on multivariable logistic regression models, dietary supplement use in women was associated with age (positively until middle-age and slightly negatively afterwards), the presence of a chronic health condition (OR = 1.71, 95% CI, 1.18–2.46), lost/removed teeth (OR = 0.52, 95% CI, 0.35–0.78) and diastolic blood pressure (OR per 5 mmHg increase =0.84, 95% CI, 0.73–0.96), body mass index and worse general health status were borderline inversely associated. In men, dietary supplement use was positively associated with being employed (OR = 2.53, 95% CI, 1.21–5.29). A considerable proportion of our sample used dietary supplements, and the associated factors differed between women and men.

Made available in DSpace on 2022-04-28T19:44:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Rijksuniversiteit Groningen Universidade Estadual Paulista Pontificia Universidad Javeriana Fondo Nacional de Desarrollo Científico y Tecnológico Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) A balanced communication between the mother, placenta and foetus is crucial to reach a successful pregnancy. Several windows of exposure to environmental toxins are present during pregnancy. When the women metabolic status is affected by a disease or environmental toxin, the foetus is impacted and may result in altered development and growth. Gestational diabetes mellitus (GDM) is a disease of pregnancy characterised by abnormal glucose metabolism affecting the mother and foetus. This disease of pregnancy associates with postnatal consequences for the child and the mother. The whole endogenous and exogenous environmental factors is defined as the exposome. Endogenous insults conform to the endo-exposome, and disruptors contained in the immediate environment are the ecto-exposome. Some components of the endo-exposome, such as Selenium, vitamins D and B12, adenosine, and a high-fat diet, and ecto-exposome, such as the heavy metals Arsenic, Mercury, Lead and Copper, and per- and polyfluoroakyl substances, result in adverse pregnancies, including an elevated risk of GDM or gestational diabesity. The impact of the exposome on the human placenta's vascular physiology and function in GDM and gestational diabesity is reviewed. Cellular and Molecular Physiology Laboratory (CMPL) Department of Obstetrics Division of Obstetrics and Gynaecology School of Medicine Faculty of Medicine Pontificia Universidad Católica de Chile Faculty of Health Sciences Universidad de Talca Faculty of Health Sciences Universidad de Antofagasta Department of Nutrition and Biochemistry Faculty of Sciences Pontificia Universidad Javeriana Metabolic Diseases Research Laboratory Interdisciplinary Centre of Territorial Health Research (CIISTe) Biomedical Research Center (CIB) San Felipe Campus School of Medicine Faculty of Medicine Universidad de Valparaíso Tecnologico de Monterrey Escuela de Medicina y Ciencias de la Salud Cátedra de Cardiología Hospital Zambrano-Hellion, TecSalud, San Pedro Garza-García Department of Obstetrics Division of Obstetrics and Gynaecology and Department of Neonatology Division of Pediatrics School of Medicine Faculty of Medicine Pontificia Universidad Católica de Chile Department of Physiology Faculty of Pharmacy Universidad de Sevilla Medical School (Faculty of Medicine) Sao Paulo State University (UNESP) University of Queensland Centre for Clinical Research (UQCCR) Faculty of Medicine and Biomedical Sciences University of Queensland Department of Obstetrics and Gynaecology University of Groningen University Medical Center Groningen (UMCG), Hanzeplein 1, Groningen Department of Pediatrics University of Groningen University Medical Center Groningen Nestlé Institute for Health Sciences, Nestlé Research, Societé des Produits de Nestlé, Lausanne 26 Department of Pathology and Medical Biology Division of Pathology University of Groningen University Medical Center Groningen (UMCG) Medical School (Faculty of Medicine) Sao Paulo State University (UNESP) Fondo Nacional de Desarrollo Científico y Tecnológico: 1190316 CAPES: 88882.432902/2019-01

Hypercalcemia of malignancy frequently occurs in patients with solid tumors as a paraneoplastic syndrome known as humoral hypercalcemia of malignancy (HHM), caused by the secretion of parathyroid hormone-related peptide (PTHrP). On the other hand, 1,25-dihydroxyvitamin D [1,25(OH)2D]-mediated hypercalcemia is a less common cause of hypercalcemia of malignancy and is mostly observed in lymphoma patients. Here, we report an interesting case of a 77-year-old male nursing home resident with suspected renal cell carcinoma (RCC) presenting with severe hypercalcemia (18.7 mg/dL), which was initially presumed to be HHM. However, workup revealed nonsuppressed parathyroid hormone, low PTHrP, and elevated 25-hydroxyvitamin D and 1,25(OH)2D levels. Steroids were initiated due to an inadequate response to bisphosphonate therapy and elevated vitamin D metabolites, resulting in further reduction in serum calcium levels. This case highlights the need to consider multiple concurrent etiologies in the differential diagnosis of severe hypercalcemia, including the possible role of calcitriol-mediated hypercalcemia in RCC.

Diabetes Mellitus type II (DM II) is a worldwide disease with a rapidly growing parallel prevalence and adversities affecting multi-body systems. Hence, it is imperative to treat DM II effectively, maintaining glucose homeostasis to avoid complications such as diabetic nephropathy, peripheral neuropathy, and retinopathy. Vitamin D, among many benefits, has positive outcomes on hemoglobin A1c (HbA1c) control. It aids in insulin secretion and sensitivity. We systematically screened four databases for relevant information; PubMed, Medline, PMC, and Google scholar. Inclusion and exclusion criteria were applied, and quality appraisal was then done using certain checklist tools: Newcastle-Ottawa tool, AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist, SANRA (Scale for the Assessment of Narrative Review Articles) checklist, and Cochrane bias assessment. Data were collected from 14 articles, of which eight are systematic reviews and meta-analysis, one is a narrative review, five are randomized controlled trials and three are general information about DM II and Vitamin D. In addition, this article evaluates the clinical significance of Vitamin D administration in DM II from a glucose homeostasis perspective, and complications such as nephropathy, neuropathy, and retinopathy. Vitamin D had a clinical positive impact on glucose level, particularly on hemoglobin A1c (HbA1c) reduction, alleviation of diabetic neuropathy and nephropathy symptoms, and hyperglycemia induced-oxidative stress on the retinal cells.

Background: Heart failure (HF) is a multifactorial syndrome with pathophysiological complexities still not fully understood. Higher mean platelet volume (MPV), a potential marker of platelet activation, and high concentrations of parathyroid hormone (PTH) have been implicated in the pathogenesis of HF.Aim: This study aims to investigate sex-specifically the association between PTH concentrations and platelet indices in phenotypes of HF.Methods and Results: PTH and platelet indices (MPV and platelet count) were available in 1,896 participants from the MyoVasc study in Mainz, Germany. Multivariable linear regression models, adjusted for age, sex, season, vitamin D status, cardiovascular risk factors, comorbidities, estimated glomerular filtration rate, and medication, were used to assess the associations between platelet indices and PTH. The results showed distinct sex-specific associations between PTH and platelet indices. A positive association between PTH and MPV was found in females with symptomatic HF with reduced ejection fraction (HFrEF) only [β = 0.60 (0.19; 1.00)]. Platelet count was inversely associated with PTH in male HFrEF individuals [β = −7.6 (−15; −0.30)] and in both males and females with HF with preserved ejection fraction (HFpEF).Conclusion: This study reports differential, sex-specific relationships between PTH and platelet indices in HF individuals independent of vitamin D status and clinical profile. Particularly in phenotypes of symptomatic HF, distinct associations were observed, suggesting a sex-specific mechanism involved in the interaction between PTH and platelets.

Background Recent efforts in the field of nutritional science have allowed the discovery of disease-beating molecules within foods based on the commonality of bioactive food molecules to FDA-approved drugs. The pioneering work in this field used an unsupervised network propagation algorithm to learn the systemic-wide effect on the human interactome of 1962 FDA-approved drugs and a supervised algorithm to predict anticancer therapeutics using the learned representations. Then, a set of bioactive molecules within foods was fed into the model, which predicted molecules with cancer-beating potential.The employed methodology consisted of disjoint unsupervised feature generation and classification tasks, which can result in sub-optimal learned drug representations with respect to the classification task. Additionally, due to the disjoint nature of the tasks, the employed approach proved cumbersome to optimize, requiring testing of thousands of hyperparameter combinations and significant computational resources.To overcome the technical limitations highlighted above, we represent each drug as a graph (human interactome) with its targets as binary node features on the graph and formulate the problem as a graph classification task. To solve this task, inspired by the success of graph neural networks in graph classification problems, we use an end-to-end graph neural network model operating directly on the graphs, which learns drug representations to optimize model performance in the prediction of anticancer therapeutics. Results The proposed model outperforms the baseline approach in the anticancer therapeutic prediction task, achieving an F1 score of 67.99%±2.52% and an AUPR of 73.91%±3.49%. It is also shown that the model is able to capture knowledge of biological pathways to predict anticancer molecules based on the molecules’ effects on cancer-related pathways. Conclusions We introduce an end-to-end graph convolutional model to predict cancer-beating molecules within food. The introduced model outperforms the existing baseline approach, and shows interpretability, paving the way to the future of a personalized nutritional science approach allowing the development of nutrition strategies for cancer prevention and/or therapeutics.

The term sarcopenia was introduced in 1988. The original definition was a “muscle loss” of the appendicular muscle mass in the older people as measured by dual energy x‐ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC‐F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease‐related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age‐related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age‐related and disease‐related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life‐long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia.

Aim: This population-based study assessed the incidence of rickets in infants up to age of one born in Sweden from 1997 to 2014. We also examined maternal and perinatal factors and co-morbidity. Methods: We used Swedish National Board of Health and Welfare registers and data from Statistics Sweden. The outcome measure was an International Classification of Diseases, Tenth Revision, code for rickets. Results: There were 273 cases of rickets, with an incidence of 14.7 per 100 000 and a 10-fold incidence increase between 1997 and 2014. The majority (78.4%) were born preterm, half were small-for-gestational age (SGA) (birthweight

Objective: We aimed to elucidate the local role of FGF23 after myocardial infarction in a mouse model induced by left anterior descending artery (LAD) ligation.Approach and results: (C57BL/6N) mice underwent MI via LAD ligation and were sacrificed at different time-points post MI. The expression and influence of FGF23 on fibroblast and macrophages was also analyzed using isolated murine cells.We identified enhanced cardiac FGF23 mRNA expression in a time-dependent manner with an early increase, already on the first day after MI. FGF23 protein expression was abundantly detected in the infarcted area during the inflammatory phase. While described to be primarily produced in bone or macrophages, we identified cardiac fibroblasts as the only source of local FGF23 production after MI. Inflammatory mediators, such as IL-1 beta, IL-6 and TNF-alpha, were able to induce FGF23 expression in these cardiac fibroblasts. Interestingly, we were not able to detect FGF23 at later time points after MI in mature scar tissue or remote myocardium, most likely due to TGF-beta 1, which we have shown to inhibit the expression of FGF23. We identified FGFR1c to be the most abundant receptor for FGF23 in infarcted myocardium and cardiac macrophages and fibroblasts. FGF23 increased migration of cardiac fibroblast, as well as expression of Collagen 1, Periostin, Fibronectin and MMP8. FGF23 also increased expression of TGF-beta 1 in M2 polarized macrophages.Conclusion: In conclusion, cardiac fibroblasts in the infarcted myocardium produce and express FGF23 as well as its respective receptors in a time-dependent manner, thus potentially influencing resident cell migration. The transitory local expression of FGF23 after MI points towards a complex role of FGF23 in myocardial ischemia and warrants further exploration, considering its role in ventricular remodeling. (C) 2019 Elsevier Inc. All rights reserved.

Background: Pulmonary arterial hypertension (PAH) is a rare, progressive disease of the pulmonary vasculature. Recent advances in pharmacotherapy improved life expectancy of PAH patients and, thus, signified the role of general measures, including diet, in the management of the disease.Methods: In the present narrative review we will briefly summarize information about current and novel PAH therapies and analyze preclinical evidence on the influence of certain nutrients on the pathogenesis of PAH.Results: Although the evidence on the role of dietary deficiencies in the development and progression of PAH in humans is limited, preclinical studies demonstrate that dietary components such as quercetin, genistein, n-3 PUFAs, vitamin D, coenzyme Q10 and resveratrol may influence various aspects of PAH pathobiology.Conclusions: Further research on the role of diet in PAH is needed. Taking into account pleiotropic and subtle effects of dietary constituents as well as the rare and severe nature of PAH, clinical studies on the disease-specific nutritional patterns rather than on single dietary components may help to reveal if diet can be an important tool to improve the efficacy of pharmacotherapy in PAH. (C) 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

The current study was focused on patients with Multiple sclerosis between the ages group of 20 - 60. The objective of this study is to decide the level of 25-hydroxyvitamin D3 status in patients with multiple sclerosis (MS) and its engagement, with disease activity. A total of 31 cases have participated from Baghdad Teaching Hospital in Baghdad, Iraq during the period between March and April 2018. The results shows that, only significant finding was that, supplements for Vitamin D significantly increased its mean level in patients with Multiple Sclerosis (P < 0.05).

Objective Hospitalization is generally accompanied by changes in food intake. Patients typically receive hospital meals upon personal preference within the framework of the food administration services of the hospital. In the present study, we assessed food provision and actual food and snack consumption in older patients admitted for elective hip or knee arthroplasty. Design A prospective observational study. Setting Orthopedic nursing ward of the Maastricht University Medical Centre+. Participants In the present study, n=101 patients (age: 67±10 y; hospital stay: 6.1±1.8 d) were monitored during hospitalization following elective hip or knee arthroplasty. Measurements Energy and protein provided by self-selected hospital meals and snacks, and actual energy and protein (amount, distribution, and source) consumed by patients was weighed and recorded throughout 1–6 days. Results Self-selected meals provided 6.5±1.5 MJ·d-1, with 16, 48, and 34 En% provided as protein, carbohydrate, and fat, respectively. Self-selected hospital meals provided 0.75±0.16 and 0.79±0.21 g·kg-1·d-1 protein in males and females, respectively. Actual protein consumption averaged merely 0.59±0.18 and 0.50±0.21 g·kg-1·d-1, respectively. Protein consumption at breakfast, lunch, and dinner averaged 16±8, 18±9, and 20±6 g per meal, respectively. Conclusions Though self-selected hospital meals provide patients with ∼0.8 g·kg-1·d-1 protein during short-term hospitalization, actual protein consumption falls well below 0.6 g·kg-1·d-1 with a large proportion (∼32%) of the provided food being discarded. Alternative strategies are required to ensure maintenance of habitual protein intake in older patients admitted for elective orthopedic surgery. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s12603-019-1157-2 and is accessible for authorized users.

In the present review, recent findings regarding autoimmune/inflammatory syndrome by adjuvants (ASIA) are described. Patients with ASIA present with complaints such as fatigue, cognitive impairment, arthralgias, myalgias, pyrexia, dry eyes and dry mouth. During the last few years, it has been postulated that these symptoms in patients with foreign body implants are due to a chronic inflammatory process and an adjuvant effect of the implanted biomaterial. Ultimately, these inflammatory reactions result in (an increase of) allergies, autoimmune diseases, immune deficiency and/or lymphomas. Pre-existent allergic disease has been found to be an important risk factor for the development of ASIA after foreign body implantation. Explantation of the foreign body results in the majority of patients in an amelioration of the symptoms. There is an urgent need to start adequately adjusted epidemiological studies to obtain better evidence which percentage of patients does develop symptoms and/or diseases such as ASIA, immune deficiency, and/or autoimmune diseases after implant surgery.

Bone grafting is one of the most commonly used options to treat large bone defects. Evidence has shown that vitamin D may affect osseointegration, a major component for successful bone grafting. In vitro studies have proved that implants coated with activated vitamin D stimulate bone production and reduce bone resorption around implants. Animal studies have noticed that oral administration of vitamin D may stimulate bone formation as well as strengthen and support the interaction between bone and implants. Vitamin D insufficiency may affect negatively the cortical peri-implant bone formation, suggesting a negative effect in graft incorporation. Few clinical studies have observed that vitamin D administration enhanced graft incorporation and bone formation, while severe vitamin D deficiency is associated with failed implant osseointegration. Even though there are encouraging results of vitamin D supplementation on graft incorporation in animal studies, the use of vitamin D as an adjuvant in bone grafting procedures cannot be fully supported at the moment. However, there is theoretical support in the use of vitamin D after surgery and the use of bone grafts to support the bone structure, relieve pain and increase graft absorption. Further experimental and clinical studies are required to support the administration of vitamin D and its analogues in such cases.

Background: Leucine-enriched protein (LEU-PRO) and long-chain(LC) n–3 (ω–3) PUFAs have each been proposed to improve muscle mass and function in older adults, whereas their combination may be more effective than either alone.Objective: The impact of LEU-PRO supplementation alone and combined with LC n–3 PUFAs on appendicular lean mass, strength, physical performance and myofibrillar protein synthesis(MyoPS) was investigated in older adults at risk of sarcopenia.Methods: This 24-wk, 3-arm parallel, randomized, double-blind, placebo-controlled trial was conducted in 107 men and women aged ≥65 y with low muscle mass and/or strength. Twice daily, participants consumed a supplement containing either LEU-PRO(3 g leucine, 10 g protein; n = 38), LEU-PRO plus LC n–3 PUFAs (0.8 g EPA, 1.1 g DHA; LEU-PRO+n–3; n = 38),or an isoenergetic control (CON; n = 31). Appendicular lean mass, handgrip strength, leg strength, physical performance, and circulating metabolic and renal function markers were measured pre-, mid-, and postintervention. Integrated rates of MyoPS were assessed in a subcohort (n = 28).Results: Neither LEU-PRO nor LEU-PRO+n–3 supplementation affected appendicular lean mass, handgrip strength, knee extension strength, physical performance or MyoPS. However, isometric knee flexion peak torque (treatment effect: −7.1 Nm; 95% CI: −12.5,−1.8 Nm; P < 0.01) was lower post supplementation in LEUPRO+n–3 compared with CON. Serum triacylglycerol and total adiponectin concentrations were lower, and HOMA-IR was higher, in LEU-PRO+n–3 compared with CON postsupplementation (allP < 0.05). Estimated glomerular filtration rate was higher and cystatin c was lower in LEU-PRO and LEU-PRO+n–3 postsupplementation compared with CON (all P < 0.05).Conclusions: Contrary to our hypothesis, we did not observe a beneficial effect of LEU-PRO supplementation alone or combined with LC n–3 PUFA supplementation on appendicular lean mass, strength, physical performance or MyoPS in older adults at risk of sarcopenia. This trial was registered at clinicaltrials.gov asNCT03429491.

Diabetes is associated with a strongly elevated risk of cardiovascular disease, which is even more pronounced in patients with diabetic nephropathy. Currently available guideline-based efforts to correct traditional risk factors are only partly able to attenuate this risk, underlining the urge to identify novel treatment targets. Emerging data point towards a role for disturbances in phosphate metabolism in diabetes. In this review, we discuss the role of phosphate and the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) in diabetes. We address deregulations of phosphate metabolism in patients with diabetes, including diabetic ketoacidosis. Moreover, we discuss potential adverse consequences of these deregulations, including the role of deregulated phosphate and glucose as drivers of vascular calcification propensity. Finally, we highlight potential treatment options to correct abnormalities in phosphate and FGF23. While further studies are needed to more precisely assess their clinical impact, deregulations in phosphate and FGF23 are promising potential target in diabetes and diabetic nephropathy.

Objective: Increased life span with regular transfusion and iron chelator treatments enhances the importance of nutrition in beta thalassemia. Controlling Nutritional Status (CONUT) score is a nutritional index calculated on serum albumin, total cholesterol and lymphocyte count. We aim to evaluate need for transfusion and the clinical conditions which cause morbidity with CONUT score in patients with adult transfusion dependent beta thalassemia (BTD). Method: We conducted a retrospective study at the Denizli Thalassemia Center. We used Mann Whitney Utest for comparing. We applied logistic regression analysis and ROC analysis to evaluate CONUT score and clinical effects. Results: A total of 102 patients with BTD were included. 89 were beta thalassemia major and 13 were transfusion dependent thalassemia intermedia (44 male,58 female). The median age was 26. The mean follow up period was 26 months. The median of CONUT score was 3.0 (min: 0-max: 6). CONUT score of 54 patients (52.9%) was high (>3). We found significant difference with CONUT score >3 (median:32 units) and CONUT score of 3) (p = 0.001). CONUT score is a distinguishing parameter for hypogonadism (p = 0.001; AUC = 0.922) and low bone mass (p = 0.001; AUC = 0.867). Conclusion: CONUT score can be used as a predictor to evaluate need for transfusion and morbidity of patients with BTD. If nutritional status is closely followed with CONUT score and nutritional deficiency is corrected, cost and complications will be decreased and expanctancy of life can be increased.

Key summary points Aim To review current cardiovascular medications for benefits and potential harms during COVID-19. Findings Several cardiovascular drugs have a potential to protect patients with COVID-19, although evidence is largely based on observational studies and age-specific data are scarce. Message Most current cardiovascular drugs can be safely continued during COVID-19, but general conditions common in older patients must be considered. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00504-5., Purpose In the pathogenesis of severe COVID-19 complications, derangements of renin–angiotensin–aldosterone system (RAAS), vascular endothelial dysfunction leading to inflammation and coagulopathy, and arrhythmias play an important role. Therefore, it is worth considering the use of currently available drugs to protect COVID-19 patients with cardiovascular diseases. Methods We review the current experience of conventional cardiovascular drugs [angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, anticoagulants, acetosalicylic acid, antiarrhythmic drugs, statins] as well as some other drug classes (antidiabetic drugs, vitamin D and NSAIDs) frequently used by older patients with cardiovascular diseases. Data were sought from clinical databases for COVID-19 and appropriate key words. Conclusions and recommendations are based on a consensus among all authors. Results Several cardiovascular drugs have a potential to protect patients with COVID-19, although evidence is largely based on retrospective, observational studies. Despite propensity score adjustments used in many analyses observational studies are not equivalent to randomised controlled trials (RCTs). Ongoing RCTs include treatment with antithrombotics, pulmonary vasodilators, RAAS-related drugs, and colchicine. RCTs in the acute phase of COVID-19 may not, however, recognise the benefits of long term anti-atherogenic therapies, such as statins. Conclusions Most current cardiovascular drugs can be safely continued during COVID-19. Some drug classes may even be protective. Age-specific data are scarce, though, and conditions which are common in older patients (frailty, comorbidities, polypharmacy) must be individually considered for each drug group. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00504-5.

Background: We investigated whether preoperative and postoperative levels of inflammation markers, which have mechanistically been linked to colorectal cancer progression, were associated with recurrence and all-cause mortality in patients with colorectal cancer. Methods: Data of two prospective cohort studies were used. For the current analysis, patients with stage I to III colorectal cancer were considered. Data on inflammation [IL6, IL8, IL10, TNFα, high-sensitivity C-reactive protein (hsCRP), and a combined inflammatory z-score] were available for 747 patients before surgery and for 614 patients after surgery. The associations between inflammation marker levels and colorectal cancer recurrence and all-cause mortality were examined using multivariable Cox proportional hazard regression models, considering patient characteristics and clinical and lifestyle factors. Results: Higher preoperative and postoperative hsCRP levels were associated with a higher risk of recurrence [HRper doubling (95% CI), 1.15 (1.02–1.30) and 1.34 (1.16–1.55)] and all-cause mortality [HRper doubling (95% CI) 1.13 (1.01–1.28) and 1.15 (0.98–1.35)]. A doubling in IL8 levels (preoperative levels HR = 1.23; 95% CI, 1.00–1.53 and postoperative levels HR = 1.61; 95% CI, 1.23–2.12) and a higher combined inflammatory z-score (preoperative HRper doubling = 1.39; 95% CI, 1.03–1.89 and postoperative HRper doubling = 1.56; 95% CI, 1.06–2.28) were associated with a higher risk of all-cause mortality, but not recurrence. No associations between IL6, IL10, and TNFα and recurrence or all-cause mortality were observed. Conclusions: Preoperative and postoperative levels of specific inflammation markers were associated with recurrence and/or all-cause mortality. Impact: The complex role of inflammation in cancer recurrence merits further elucidation by investigating local inflammation at the tumor site.

Asthma is a chronic inflammatory disease of the airways, characterized by T-helper (Th) 2 inflammation. Current lifestyle recommendations for asthma patients are to consume a diet high in fruits and vegetables and to maintain a healthy weight. This raises the question of whether other nutritional interventions may also improve asthma-related outcomes and whether these changes occur via immunomodulation. Therefore, we systematically reviewed studies that reported both asthma-related outcomes as well as immunological parameters and searched for relations between these two domains. A systematic search identified 808 studies, of which 28 studies met the inclusion criteria. These studies were divided over six nutritional clusters: herbs, herbal mixtures and extracts (N = 6); supplements (N = 4); weight loss (N = 3); vitamin D3 (N = 5); omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) (N = 5); and whole-food approaches (N = 5). Fifteen studies reported improvements in either asthma-related outcomes or immunological parameters, of which eight studies reported simultaneous improvements in both domains. Two studies reported worsening in either asthma-related outcomes or immunological parameters, of which one study reported a worsening in both domains. Promising interventions used herbs, herbal mixtures or extracts, and omega-3 LCPUFAs, although limited interventions resulted in clinically relevant results. Future studies should focus on further optimizing the beneficial effects of nutritional interventions in asthma patients, e.g., by considering the phenotypes and endotypes of asthma.

Background Guidelines on laboratory screening in schizophrenia recommend annual monitoring of fasting lipids and glucose. The utility and the cost effectiveness of more extensive laboratory screening have not been studied. Methods The Living Conditions and the Physical Health of Outpatients with Schizophrenia Study provided a comprehensive health examination, including a laboratory test panel for 275 participants. We calculated the prevalence of the results outside the reference range for each laboratory test, and estimated the cost effectiveness to find an aberrant test result using the number needed to screen to find one abnormal result (NNSAR) and the direct cost spent to find one abnormal result (DCSAR, NNSAR x direct cost per test) formulas. In addition, we studied whether patients who were obese or used clozapine had more often abnormal results. Results A half of the sample had 25-hydroxyvitamin D below, and almost one-fourth cholesterol, triglycerides or glucose above the reference range. One-fifth had sodium below and gamma glutamyltransferase above the reference range. NNSAR was highest for potassium (137) and lowest for 25-hydroxyvitamin D (2). DCSAR was below 5€ for glucose, all lipids and sodium, and below 10€ for creatinine and gamma glutamyltransferase. Potassium (130€), pH-adjusted ionized calcium (33 €) and thyroid stimulating hormone (33€) had highest DCSARs. Several abnormal results were more common in obese and clozapine using patients. Conclusions An annual laboratory screening panel for an outpatient with schizophrenia should include fasting glucose, lipids, sodium, creatinine, a liver function test and complete blood count, and preferably 25-hydroxyvitamin D.

Objective:To investigate whether adherence to the adapted Mediterranean Diet Score for Adolescents (MDS_A) and the adapted Mediterranean Diet Quality Index for Adolescents (KIDMED_A) is associated with better food/nutrient intakes and nutritional biomarkers.Design:The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study is a cross-sectional study aiming to obtain comparable data on a variety of nutritional and health-related parameters in European adolescents aged 12·5–17·5 years.Setting:Nine European countries.Participants:European adolescents (n 2330) recruited to the HELENA study. Dietary intake was obtained with 24 h dietary recalls, an FFQ and a Food Choices and Preferences questionnaire. MDS_A was calculated as a categorical variable using cut-offs (MDS_A), as a continuous variable (zMDS_A) and with energy adjustments (zEnMDS_A). The KIDMED_A score was also calculated.Results:Multilevel linear regression analysis showed positive associations for zMDS_A and KIDMED_A with serum levels of vitamin D, vitamin C, plasma folate, holo-transcobalamin, β-carotene and n-3 fatty acids, while negative associations were observed with trans-fatty acid serum levels. For categorical indices, blood biomarkers showed few significant results. zMDS_A and KIDMED_A showed positive associations with vegetables and fruits intake, and negative associations with energy-dense and low-nutritious foods. zMDS_A and KIDMED_A were positively associated with all macronutrients, vitamins and minerals (all P < 0·0001), except with monosaccharides and PUFA for KIDMED_A and cholesterol for both indices (P < 0·05).Conclusions:zMDS_A and KIDMED_A have shown the strongest associations with the dietary indicators and biomarkers that have been associated with the Mediterranean diet before, and are therefore considered the most appropriate and valid Mediterranean diet scores for European adolescents.

Background: We previously showed that daily consumption of a multi-ingredient nutritional supplement increased lean mass in older men, but did not enhance lean tissue gains during a high-intensity interval training (HIIT) plus resistance exercise training (RET) program. Here, we aimed to determine whether these divergent observations aligned with the myofibrillar protein synthesis (MyoPS) response to acute unaccustomed and accustomed resistance exercise. Methods: A sub-sample of our participants were randomly allocated (n = 15; age: 72 ± 7 years; BMI: 26.9 ± 3.1 kg/m2 [mean ± SD]) to ingest an experimental supplement (SUPP, n = 8: containing whey protein, creatine, vitamin D, and n-3 PUFA) or control beverage (CON, n = 7: 22 g maltodextrin) twice per day for 21 weeks. After 7 weeks of consuming the beverage alone (Phase 1: SUPP/CON only), subjects completed 12 weeks of RET (twice per week) + HIIT (once per week) (Phase 2: SUPP/CON + EX). Orally administered deuterated water was used to measure integrated rates of MyoPS over 48 h following a single session of resistance exercise pre- (unaccustomed) and post-training (accustomed). Results: Following an acute bout of accustomed resistance exercise, 0-24 h MyoPS was 30% higher than rest in the SUPP group (effect size: 0.86); however, in the CON group, 0-24 h MyoPS was 0% higher than rest (effect size: 0.04). Nonetheless, no within or between group changes in MyoPS were statistically significant. When collapsed across group, rates of MyoPS in recovery from acute unaccustomed resistance exercise were positively correlated with training-induced gains in whole body lean mass (r = 0.63, p = 0.01). Conclusion: There were no significant between-group differences in MyoPS pre- or post-training. Integrated rates of MyoPS post-acute exercise in the untrained state were positively correlated with training-induced gains in whole body lean mass. Our finding that supplementation did not alter 0-48 h MyoPS following 12 weeks of training suggests a possible adaptive response to longer-term increased protein intake and warrants further investigation. This study was registered at ClinicalTrials.gov. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02281331.

Highlights • The vitamin D endocrine system have a variety of actions on cells and tissues involved in COVID-19 progression. • Early calcifediol (25-hydroxyvitamin D) treatment to hospitalized COVID-19 patients significantly reduced intensive care unit admissions-Calcifediol seems to be able to reduce severity of the COVID-19. • Calcifediol seems to be able to reduce severity of the disease., Objective The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. Design Parallel pilot randomized open label, double-masked clinical trial. Setting University hospital setting (Reina Sofia University Hospital, Córdoba Spain.) Participants 76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1). Procedures All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths. Results Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002−0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged. Conclusion Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.

Purpose of Review Fibroblast growth factor 23 (FGF23) is a key phosphate-regulating hormone that has been associated with adverse outcomes in patients with chronic kidney disease (CKD). Emerging data suggest that FGF23 plays a specific role in type 2 diabetes, partly independent of kidney function. We aimed to summarize current literature on the associations between FGF23 and outcomes in patients with type 2 diabetes with or without CKD. Recent Findings Several cohort studies have shown strong associations between plasma FGF23 and cardiovascular outcomes in diabetic CKD. Moreover, recent data suggest that FGF23 are elevated and may also be a risk factor for cardiovascular disease and mortality in type 2 diabetes patients without CKD, although the magnitude of the association is smaller than in CKD patients. Summary Diabetes-related factors may influence plasma FGF23 levels, and a higher FGF23 levels seem to contribute to a higher cardiovascular and mortality risk in patients with type 2 diabetes. Although this risk may be relevant in diabetic individuals with preserved kidney function, it is strongly accentuated in diabetic nephropathy. Future studies should clarify if FGF23 is merely a disease severity marker or a contributor to adverse outcomes in type 2 diabetes and establish if antidiabetic medication can modify FGF23 levels.

BACKGROUND: Many studies have shown low Vitamin-D level as a risk factor for autoimmune diseases, especially multiple sclerosis and thyroid disease. Graves’ disease (GD) is an autoimmune disease caused by autoantibodies that stimulate thyroid-stimulating hormone (TSH) receptors by increasing thyroid hormone synthesis and secretion. Several studies report that many patients with autoimmune thyroid disease including GD have low Vitamin-D status. AIM: The objective of the study was to evaluate the effect of Vitamin-D supplement on GD patients on improvement in thyroid hormone levels. METHODS: Open random clinical trial was conducted in GD patients to determine changes in thyroid hormone to achieving normal levels between those receiving methimazole plus Vitamin-D supplementation compared with those who only received methimazole. Patients were checked for TSH receptor antibody, thyroid profile and Vitamin-D level before treatment and rechecked for thyroid profile and Vitamin-D level 3 months after treatment. t-test used to compare the drug efficacy (p < 0.05) in two groups. RESULTS: From 25 children with GD accompanied by Vitamin-D deficiency with an average value of Vitamin-D was 16 ng/mL. GD children who receive methimazole with Vitamin-D supplement had elevated TSH levels in the 3rd month of therapy that was significantly different compared to GD children who received methimazole only (p = 0.00), and the increase of TSH was also followed by an increase in Vitamin-D levels. CONCLUSION: All children with GD had Vitamin D deficiency, and the addition of Vitamin-D supplement to GD therapy would improve TSH faster than children who did not receive Vitamin-D supplement.

Systemic sclerosis (SSc) is a connective tissue disease characterized by initial microvascular damage, immune system activation and progressive fibrosis with insufficiency of internal organs. Gastrointestinal (GI) involvement is characterized by atrophy of the smooth muscle and small bowel hypomotility, mainly resulting from an autonomic nerve dysfunction. These modifications significantly affect gut transit and nutrient absorption, thus leading to malnutrition deficit induced by malabsorption. Nutritional deficit induced by malabsorption might also lead to bone alterations. This study aims to evaluate the relationship between malnutrition and bone status. Thirty-six postmenopausal female patients fulfilling the ACR 2013 criteria for SSc underwent dual-energy X-ray absorptiometry scan (DXA) to detect quantitative lumbar spine bone mineral density (BMD) and trabecular bone score (TBS) analysis to detect bone quality. Data from DXA also allow to assess body composition and provide several quantitative parameters, including free fat mass index (FFMI) that identifies the patient with malnutrition (values &lt, 15 kg/m2 in women and 17 kg/m2 in men), according to the ESPEN criteria. Body mass index (BMI) was calculated for all SSc patients and every patient completed a diary reporting GI symptoms. Two groups of SSc patients with or without diagnosed malnutrition according to FFMI parameter were identified. Malnourished SSc patients showed significantly lower weight (p = 0.01) and BMI (p = 0.001), as well as lower serum levels of hemoglobin (p = 0.009), albumin (p = 0.002), PTH (p = 0.02) and 25OH-vitamin D (p = 0.008). DXA analysis showed significantly lower lumbar L1-L4 T-score (p = 0.009) and BMD values (p = 0.029) in malnourished SSc patients. Consistently, TBS values were significantly lower in malnourished patients (p = 0.008) and correlated with BMD (at any site) and serum albumin levels (p = 0.02). In addition, FFMI positively correlated with bone parameters as well as with symptoms of intestinal impairment in malnourished SSc patients. Finally, GI symptoms significantly correlated with BMD but not with TBS. This pilot study shows that in malnourished SSc patients (2015 ESPEN criteria: FFMI&lt, 15 kg/m2), an altered bone status significantly correlates with GI involvement, in terms of symptoms being mainly due to intestinal involvement together with the presence of selected serum biomarkers of malnutrition.

CNS inflammation is a major driver of MS pathology. Differential immune responses, including the adaptive and the innate immune system, are observed at various stages of MS and drive disease development and progression. Next to these immune-mediated mechanisms, other mediators contribute to MS pathology. These include immune-independent cell death of oligodendrocytes and neurons as well as oxidative stress-induced tissue damage. In particular, the complex influence of oxidative stress on inflammation and vice versa makes therapeutic interference complex. All approved MS therapeutics work by modulating the autoimmune response. However, despite substantial developments in the treatment of the relapsing-remitting form of MS, approved therapies for the progressive forms of MS as well as for MS-associated concomitants are limited and much needed. Here, we summarize the contribution of inflammation and oxidative stress to MS pathology and discuss consequences for MS therapy development.

As a result of the current demographics, increased projections of osteoporosis (OP) and prevalence of the disease in Turkey, a panel of multidisciplinary experts developed a thorough review to assist clinicians in identifying OP and associated fracture risk patients, diagnosing the disease with the appropriate available diagnostic methods, classifying the disease, and initiating appropriate treatment. the panel expects to increase the awareness of this prevalent disease, decrease consequences of OP with corresponding cost savings and, ultimately, decrease the overall burden of OP and related fractures in Turkey. Background OP is not officially accepted as a chronic disease in Turkey despite the high prevalence and predicted increase in the following years. However, there are areas where the country is performing well, such as having a country-specific fracture risk assessment model, DXA access, and the uptake of FRAX. Additional efforts are required to decrease the existing treatment gap estimating 75-90% of patients do not receive pharmacological intervention for secondary prevention, and the diagnosis rate is around 25%. Methods A selected panel of Turkish experts in fields related to osteoporosis was provided with a series of relevant questions to address prior to the multi-day conference. Within this conference, each narrative was discussed and edited by the entire group, through numerous drafts and rounds of discussion until a consensus was achieved. Represented in the panel were a number of societies including the Turkish Osteoporosis Society, the Society of Endocrinology and Metabolism of Turkey (SEMT), and the Turkish Society of Physical Medicine and Rehabilitation. Results Standardized general guidelines to identify OP and related fractures and at-risk population in Turkey, which will enable clinicians to accurately and effectively diagnose the disease, treat the appropriate patients with available pharmacological and non-pharmacological treatments and decrease the burden of the disease. Conclusions This manuscript provides a review of the current state of OP and related fractures in Turkey. Moreover, this manuscript reviews current international guidelines and national studies and proposes a number of helpful country-specific classifications that can be used by healthcare providers caring for the at-risk population. Additionally, the panel proposes practical recommendations that should be implemented nationally in order to decrease the burden of OP and related fractures and effectively preventing the burden in future generations., Americas Health Foundation (AHF), a 501(c)3 nonprofit organization; AmgenAmgen, The manuscript was supported by a grant from the Americas Health Foundation (AHF), a 501(c)3 nonprofit organization dedicated to improving healthcare, and by unrestricted grants from Amgen.

The aim of this study was to gain insight into the nutritional status, dietary intake and muscle health of older Dutch hip fracture patients to prevent recurrent fractures and to underpin rehabilitation programs. This cross-sectional study enrolled 40 hip fracture patients (mean ± SD age 82 ± 8.0 years) from geriatric rehabilitation wards of two nursing homes in the Netherlands. Assessments included nutritional status (Mini Nutritional Assessment), dietary intake on three non-consecutive days which were compared with Dietary Reference Intake values, and handgrip strength. Muscle mass was measured using Bioelectrical Impedance Analysis and ultrasound scans of the rectus femoris. Malnutrition or risk of malnutrition was present in 73% of participants. Mean energy, protein, fibre and polyunsaturated fat intakes were significantly below the recommendations, while saturated fat was significantly above the UL. Protein intake was

Contains fulltext : 229397.pdf (Publisher’s version ) (Open Access) BACKGROUND: Persons with Lynch syndrome (LS) have an increased risk of developing colorectal tumors (CRTs). Adherence to diet quality indices associated with colorectal cancer (CRC) risk in the general population has not been studied before in LS. METHODS: Dietary habits of 490 participants with LS from a prospective cohort study was collected using a food frequency questionnaire. The Dutch Healthy Diet index 2015 (DHD15-index) and Dietary Approaches to Stop Hypertension (DASH) were used to score food-based diet quality. Diet quality scores were divided into tertiles where a higher tertile reflects a higher diet quality. Multivariable Cox proportional hazard regression models were used to estimate the association between the DHD15-index, DASH score and CRT risk. RESULTS: During a median follow-up time of 53.4 months, 210 participants (42.9%) developed CRTs. The DHD-index and DASH score were not associated with CRT risk; hazard ratios for highest vs. lowest tertile were 1.00 (95% Confidence Interval (CI): 0.67-1.48) and 1.11 (95% CI: 0.74-1.69), respectively. No linear trends across the DHD-index and DASH score tertiles were observed (P-trend = 0.97 and 0.83 respectively). CONCLUSION: In contrast to observations in the general population, no evidence for an association between the food-based DHD15-index or DASH score and CRT risk was observed in persons with LS. Further studies are needed investigating the association between diet quality and mechanisms leading to the development of LS-associated tumors.

This case report describes the clinical presentation, the necropsy findings, and genetic results of a 13‐year‐old Warmblood mare presented with colic and a bilaterally loud, holosystolic murmur. Echocardiographic examination revealed the presence of a thoracic aortic aneurysm, an aortic pseudoaneurysm, a periaortic hematoma (circumferential cuffing by perivascular hemorrhage), and aortopulmonary fistulation. A supravalvular aortic stenosis (SVAS) was visible during echocardiography. Necropsy confirmed that the thoracic aortic aneurysm had ruptured and connected to the pseudoaneurysm, which fistulated into the pulmonary artery. Histologically, the aneurysm wall revealed chronic lesions such as fibrosis, mucin depositions, mineralizations, and elastin fragmentation. The mid abdominal aorta showed lesions suggestive of a systemic elastin arteriopathy. Molecular analysis, however, could not attribute this disease to a variant in the elastin gene, the most common causative gene for SVAS. To the authors' knowledge, this case report describes a case of aortopulmonary fistulation in a Warmblood horse associated with the presence of SVAS and an aortic aneurysm.

Phosphate metabolism is an evolving area of basic and clinical research. In the past 15 years, knowledge on disturbances of phosphate homoeostasis has expanded, as has the discovery of new targeted therapies. Hypophosphataemia might be the biochemical finding in several diseases, and its clinical evaluation should initially focus on the assessment of pathophysiological mechanisms leading to low serum phosphate concentrations. Clinical consequences of hypophosphataemia can involve multiple organ systems and vary depending on several factors, the most important being the underlying disorder. This Review focuses on the approach to patients with hypophosphataemia and how underlying pathophysiological mechanisms should be understood in the evaluation of differential diagnosis. We define an algorithm for the assessment of hypophosphataemia and review the most up-to-date literature on specific therapies. Continuous research in this area will result in a better understanding and management of patients with hypophosphataemia.

Objective: Carotid-femoral pulse wave velocity (cfPWV) was associated with serum parathyroid hormone (PTH) in untreated Chinese. We investigated in the same cohort whether cfPWV, brachial-ankle (baPWV) and heart-brachial (hbPWV) pulse wave velocity (PWV) were associated with rs6127099 (CYP24A1) and rs4074995 (RGS14). A previously published genome-wide association study demonstrated that each additional copy of the T (rs6127099) or G (rs4074995) allele was associated with a 7% or 3% higher serum PTH, respectively.Methods: In 1601 untreated Chinese patients (mean age, 51.0 years; 51.9% women), we measured cfPWV by tonometry (SphygmoCor) and baPWV and hbPWV by combined oscillometry and plethysmography (VP-2000 PWV/ABI analyser), serum PTH by an immunoassay, and genotypes by the SNapShot method.Results: cfPWV, baPWV and hbPWV averaged 7.9, 14.6 and 5.5 m/s and serum PTH 65.7pg/mL. Genotype frequencies were in Hardy-Weinberg equilibrium, amounting to 41.7% (AA), 44.9% (AT) and 13.4% (TT) for rs6127099 and to 70.7% (GG), 26.9% (GA) and 2.3% (AA) for rs4074995. With adjustments applied for sex, age, body mass index, heart rate and season, hbPWV was 0.05 m/s (p=.042) lower with each additional copy of the minor allele (T) of rs6127099. In similarly adjusted analyses of 157 normotensive participants younger than 50 years, cfPWV was 0.32 m/s (p=.004) higher per additional copy of the T allele. Sensitivity analyses additionally accounting for the total-to-HDL serum cholesterol ratio, plasma glucose, glomerular filtration rate and 24h systolic blood pressure were consistent. No other association of PWV with the genetic variants reached significance.Conclusions: With an increasing number of rs6127099 T alleles, arterial stiffness, as exemplified by PWV, was lower in all participants in a muscular artery (hbPWV), but higher in young normotensive participants in an elastic artery (cfPWV).

Background: Preterm infants are at risk for impaired bone mineralization and growth in length later in life due to inadequate nutritional intake in the early postnatal period. Objective: To investigate whether increased nutritional supplementation of calcium, phosphate and protein in Very Low Birth Weight (VLBW) infants during the first 14 days after birth was associated with improvement in length and bone development until 9-10 years of age. Design: Observational follow-up study of VLBW infants (birth weight< 1500 g or gestational age < 32 weeks) born in two consecutive years (eligible infants: 2004 n: 63 and 2005: n: 66). Cohort 2005 received higher intake of calcium, phosphate and protein with parenteral nutrition compared to Cohort 2004. Anthropometric data were collected during standard follow-up visits until five years, and additionally at 9-10 years of age including measurements of bone mineral content, bone mineral density of the whole body and lumbar spine determined by dual-energy X-ray absorptiometry. Long-term growth trajectories of both cohorts were evaluated separately for participants born appropriate (AGA) and small for gestational age (SGA), stratified by gender. Multivariate linear regression was used to examine the effect of nutritional intalce and clinical covariates on length and bone mineralization. Results: Both cohorts achieved a catch-up in length to SDS within the normal range by 6 months (length SDS: estimated mean (95% confidence interval (CI): 6 months: Cohort 2004: -0.7 ( -1.1, -0.3) Cohort 2005: -0.5 (-0.8, -0.2)). Bone mineral content and density were within the normal range and not different between the cohorts. SGA children achieved a catch-up in length at 5 years with bone mineralization comparable to AGA children. Only for girls birth weight was significantly associated with length SDS (per gram: beta 0.001; 95% CI (0.000, 0.003); p = 0.03) There was no evidence of an association between early nutritional intake and bone mineralization. Conclusion: Children born as appropriate or small for gestational age preterm infants are able to catch up in length after the postnatal period, and achieve a normal length and bone mineralization at age nine-ten years. An improvement of calcium and phosphate intake during the first 14 days after birth was not associated with improvement in length and bone development. (C) 2017 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license

Background Macroalbuminuria predicts renal and cardiovascular events in patients with type 2 diabetes. We aimed to assess the albuminuria-lowering effects of salt restriction, paricalcitol therapy, or both, in this population.Methods In this randomised, double-blind, placebo-controlled, crossover trial, we recruited adult patients with type 2 diabetes from six diabetology outpatient clinics in northern Italy, with 24 h albuminuria of more than 300 mg despite 100 mg per day losartan therapy, blood pressure of less than 140/90 mm Hg, serum creatinine concentration of less than 2 mg/dL, stable renal function on stable renin-angiotensin system inhibitor therapy with a fixed dose of losartan, parathyroid hormone concentration of 20 pg/mL to 200 mEq [4.8 g] per day) or low-sodium (Findings Between Dec 13, 2011, and Feb 17, 2015, we randomly allocated 57 (50%) patients to a low-sodium diet (28 [49%] to paricalcitol then placebo and 29 [51%] to placebo then paricalcitol) and 58 (50%) to a high-sodium diet (29 [50%] to paricalcitol then placebo and 29 [50%] to placebo then paricalcitol). In the low-sodium group (30 mEq of daily sodium intake reduction, equivalent to approximately 1.7-1.8 g per day), 24 h albuminuria was reduced by 36.6% (95% CI 28.5-44.9) from 724 mg (441-1233) at baseline to 481 mg (289-837) at month 3 (pInterpretation In patients with macroalbuminuria and type 2 diabetes, moderate salt restriction enhances the antialbuminuric effect of losartan, an effect that could be nephroprotective and cardioprotective in the long term. The finding that paricalcitol prevents a sodium-induced increase in albuminuria provides support for trials to test the longterm risk-benefit profile of paricalcitol add-on therapy in patients with type 2 diabetes and macroalbuminuria refractory to dietary salt restriction, including patients refractory to even moderate salt restriction.

Novel coronavirus 2019 (COVID-19) is a zoonosis that revised the global economic and societal progress since early 2020. The SARS-CoV-2 has been recognized as the responsible pathogen for COVID-19 with high infection and mortality rate potential. It has spread in 192 countries and infected about 1.5% of the world population, and still, a proper therapeutic approach is not unveiled. COVID-19 indication starts with fever to shortness of breathing, leading to ICU admission with the ventilation support in severe conditions. Besides the symptomatic mainstay clinical therapeutic approach, only Remdesivir has been approved by the FDA. Several pharmaceutical companies claimed different vaccines with exceptionally high efficacy (90–95%) against COVID-19; how long these vaccines can protect and long-term safety with the new variants are unpredictable. After the worldwide spread of the COVID-19 pandemic, numerous clinical trials with different phases are being performed to find the most appropriate solution to this condition. Some of these trials with old FDA-approved drugs showed promising results. In this review, we have precisely compiled the efforts to curb the disease and discussed the clinical findings of Ivermectin, Doxycycline, Vitamin-D, Vitamin-C, Zinc, and cannabidiol and their combinations. Additionally, the correlation of these molecules on the prophylactic and diseased ministration against COVID-19 has been explored., Graphical Abstract ga1