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Association between characteristics at birth, breastfeeding and obesity in 22 countries: the WHO European Childhood Obesity Surveillance Initiative – COSI 2015/2017
Get PDFObjectives: It was the aim of this paper to investigate the association of early-life factors, namely breastfeeding, exclusive breastfeeding and birth weight, with obesity among children.
----- Method: Data from 22 participating countries in the WHO European COSI study (round 4: 2015/2017) were collected using cross-sectional, nationally representative samples of 6- to 9-year-olds (n = 100,583). The children's standardized weight and height measurements followed a common WHO protocol. Information on the children's birth weight and breastfeeding practice and duration was collected through a family record form. A multivariate multilevel logistic regression analysis regarding breastfeeding practice (both general and exclusive) and characteristics at birth was performed.
----- Results: The highest prevalence rates of obesity were observed in Spain (17.7%), Malta (17.2%) and Italy (16.8%). A wide between-country disparity in breastfeeding prevalence was found. Tajikistan had the highest percentage of children that were breastfed for ≥6 months (94.4%) and exclusively breastfed for ≥6 months (73.3%). In France, Ireland and Malta, only around 1 in 4 children was breastfed for ≥6 months. Italy and Malta showed the highest prevalence of obesity among children who have never been breastfed (21.2%), followed by Spain (21.0%). The pooled analysis showed that, compared to children who were breastfed for at least 6 months, the odds of being obese were higher among children never breastfed or breastfed for a shorter period, both in case of general (adjusted odds ratio [adjOR] [95% CI] 1.22 [1.16-1.28] and 1.12 [1.07-1.16], respectively) and exclusive breastfeeding (adjOR [95% CI] 1.25 [1.17-1.36] and 1.05 [0.99-1.12], respectively). Higher birth weight was associated with a higher risk of being overweight, which was reported in 11 out of the 22 countries. Bulgaria, Croatia, France, Italy, Poland and Romania showed that children who were preterm at birth had higher odds of being obese, compared to children who were full-term babies.
----- Conclusion: The present work confirms the beneficial effect of breastfeeding against obesity, which was highly increased if children had never been breastfed or had been breastfed for a shorter period. Nevertheless, adoption of exclusive breastfeeding is below global recommendations and far from the target endorsed by the WHO Member States at the World Health Assembly Global Targets for Nutrition of increasing the prevalence of exclusive breastfeeding in the first 6 months up to at least 50% by 2025
Effect of Alirocumab on Stroke in ODYSSEY OUTCOMES
Get PDFBackground: Lowering of atherogenic lipoproteins, including low-density lipoprotein cholesterol (LDL-C), reduces the risk of ischemic stroke. However, concerns have been raised about very low LDL-C levels and a potential increased risk of hemorrhagic stroke. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, despite intensive statin therapy, targeting LDL-C levels of 25 to 50 mg/dL and avoiding sustained LDL-C <15 mg/dL. This prespecified analysis was designed to assess the effect of alirocumab on ischemic and hemorrhagic stroke. We hypothesized that for patients treated with alirocumab there would be a reduction in risk of ischemic stroke without increasing hemorrhagic stroke, irrespective of baseline LDL-C and of history of cerebrovascular disease. -----
Methods: Patients were randomized to alirocumab or placebo 1 to 12 months after acute coronary syndrome. The risk of nonfatal or fatal ischemic or hemorrhagic stroke was evaluated, stratified by baseline LDL-C concentration and history of cerebrovascular disease. A potential association of very low achieved LDL-C with alirocumab treatment at month 4 and subsequent hemorrhagic stroke was assessed. -----
Results: Median follow-up was 2.8 years. In total, 263 ischemic and 33 hemorrhagic strokes occurred. Alirocumab reduced the risk of any stroke (HR, 0.72 [95% CI, 0.57-0.91]) and ischemic stroke (HR, 0.73 [95% CI, 0.57-0.93]) without increasing hemorrhagic stroke (HR, 0.83 [95% CI, 0.42-1.65]). In total, 7164 (37.9%), 6128 (32.4%), and 5629 (29.7%) patients had a baseline LDL-C of 100 mg/dL, respectively. The treatment effect on stroke appeared numerically greater for patients with higher baseline LDL-C, but there was no formal evidence of heterogeneity (Pinteraction=0.31). The effect of alirocumab on stroke was similar among 944 patients (5.0%) with a history of previous cerebrovascular disease and among those without a history of cerebrovascular disease (Pinteraction=0.37). There was no apparent adverse relation between lower achieved LDL-C and incidence of hemorrhagic stroke in the alirocumab group. -----
Conclusions: In patients with recent acute coronary syndrome and dyslipidemia despite intensive statin therapy, alirocumab decreased the risk of stroke, irrespective of baseline LDL-C and history of cerebrovascular disease, over a median follow-up of 2.8 years. Furthermore, risk of hemorrhagic stroke did not depend on achieved LDL-C levels within the alirocumab group
Immune and autonomic nervous system interactions in multiple sclerosis: clinical implications
Get PDFMultiple sclerosis is characterized by a wide spectrum of clinical manifestations, among which dysfunction of the autonomic nervous system represents an important cause of multiple sclerosis-related disability. The aim of this review is to provide an overview of autonomic dysfunction in people with multiple sclerosis, and to discuss the interactions between the immune and autonomic nervous systems and the effects of these interactions on various aspects of multiple sclerosis. Autonomic dysfunction in people with multiple sclerosis can be demonstrated clinically and on a molecular level. Clinically, it can be demonstrated by measuring autonomic symptoms with the Composite Autonomic Symptom Score (COMPASS-31), and neurophysiologically, with different autonomic nervous system tests. Both symptomatic and objectively determined autonomic dysfunction can be associated with increased risk of multiple sclerosis disease activity. Further supporting these clinical observations are molecular changes in immune cells. Changes in the sympathetic autonomic system, such as different expression of dopaminergic and adrenergic receptors on immune cells, or modulation of the cholinergic anti-inflammatory pathway over different subunits of the nicotinic acetylcholine receptor in the peripheral immune system, may mediate different effects on multiple sclerosis disease activity
Human neuroblastoma SH-SY5Y cells treated with okadaic acid express phosphorylated high molecular weight tau-immunoreactive protein species
Get PDFBackground: Early stages of Alzheimer's disease (AD) are characterized by high phosphorylation of microtubule-associated protein tau, which may result from the downregulation of protein phosphatases. -----
New method: In order to model phosphatase downregulation and analyze its effect on tau aggregation in vitro, we treated neuroblastoma SH-SY5Y cells with okadaic acid (OA), a protein phosphatase inhibitor, and examined high molecular weight phospho-tau species. -----
Results and comparison with existing methods: OA treatment led to the appearance of heat-stable protein species with apparent molecular weight around 100 kDa, which were immunoreactive to anti-tau antibodies against phosphorylated Ser202 and Ser396. As these high molecular weight tau-immunoreactive proteins (HMW-TIPs) corresponded to the predicted size of two tau monomers, we considered the possibility that they represent phosphorylation-induced tau oligomers. We attempted to dissociate HMW-TIPs by urea and guanidine, as well as by alkaline phosphatase treatment, but HMW-TIPs were stable under all conditions tested. These characteristics resemble properties of certain sodium dodecyl sulfate (SDS)-resistant tau oligomers from AD brains. The absence of HMW-TIPs detection by anti-total tau antibodies Tau46, CP27 and Tau13 may be a consequence of epitope masking and protein truncation. Alternatively, HMW-TIPs may represent previously unreported phosphoproteins cross-reacting with tau. -----
Conclusions: Taken together, our data provide a novel characterization of an OA-based cell culture model in which OA induces the appearance of HMW-TIPs. These findings have implications for further studies of tau under the conditions of protein phosphatase downregulation, aiming to explain mechanisms involved in early events leading to AD
Karakterizacija reakcije osteoklastnih progenitora i pojačane osteoresorpcije u mišjem modelu reumatoidnoga artritisa [Characterization of osteoclast progenitor responses and increased osteoresorption in mouse model of rheumatoid arthritis]
Get PDFOsteoclasts, specialized bone resorbing cells of hematopoietic origin, become overactive in rheumatoid arthritis, leading to bone loss and joint destruction. Osteoclast progenitor cells (OCP) arise from myeloid precursors of monocyte/macrophage lineage and are normally present in the bone marrow and among circulatory monocytes. Under inflammatory conditions their subpopulations get attracted to inflamed sites by yet unknown mechanisms and chemotactic signals. Here, we investigated frequencies and chemokine receptor expression of OCP subpopulations in circulation and periarticular bone marrow (PBM) of C57BL/6 mice with collagen induced arthritis (CIA). We found both lymphoid-negative CD45+CD11b+CD115+ and lymphoid-negative CD45+CD11b-/loCD115+ subsets of OCPs to be increased in blood and PBM of affected joints in CIA. Chemokine receptors were increasingly expressed by both mentioned OCP subsets in CIA, with substantial expression of CCR2 and CX3CR1, and lower expression of CCR1, CCR3, CCR5, CCR9 and CXCR4. CCL2 serum levels, and gene expression for TNF-α, IL-1β, IL-6 and CCL2 in affected areas and spleen were significantly increased in CIA. PBM population of OCP increasingly migrated toward CCL2 chemotactic gradient, whereas down-regulation of CCR2 expression by siRNA significantly reduced the migration potential. Intravascular in vivo staining demonstrated increased recirculation of CD45+CD11b+ cells through PBM and hind paws in CIA, with the ability of tissue homing after adoptive transfer. These results suggest that highly induced OCP subpopulations in CIA migrate to inflamed joints due to chemotaxis and therefore blocking of chemokine signaling may reduce osteoclast activity in arthritis
Validation of the new classification criteria for systemic lupus erythematosus on a patient cohort from a national referral center: a retrospective study
Get PDFAIM:
To validate Systemic Lupus International Collaborating Clinics (SLICC)-12 and American College of Rheumatology (ACR)-97 classification criteria on a patient cohort from the University Hospital Center Zagreb. ----- METHODS:
This retrospective study, conducted from 2014 to 2016, involved 308 patients with systemic lupus erythematosus (SLE) (n=146) and SLE-allied conditions (n=162). Patients' medical charts were evaluated by an expert rheumatologist to confirm the clinical diagnosis, regardless of the number of the ACR-97 criteria met. Overall sensitivity and specificity, as well as the sensitivity and specificity according to disease duration, were compared between ACR-97 and SLICC-12 classifications. Predictive value for SLE for both classifications was assessed using logistic regression and receiver operating characteristic (ROC) curves. ----- RESULTS:
The SLICC-12 criteria had significantly higher sensitivity in early disease, which increased with disease duration. The ACR-97 criteria had higher specificity. The specificity of the SLICC-12 criteria was low and decreased with disease duration. Regression analysis demonstrated the superiority of the SLICC-12 classification criteria over the ACR-97 criteria, with areas under the ROC curve of 0.801 and 0.780, respectively. ----- CONCLUSION:
Although the SLICC-12 criteria were superior to the ACR-97 and were more sensitive for diagnosing early SLE, their specificity in our population was too low. The sensitivity of the SLICC-12 classification is increased by better defined clinical features within each criterion. Our results contribute to the current initiative for developing new criteria for SLE
N-glikozilacija imunoglobulina G u kroničnoj bolesti presatka protiv primatelja nakon presadbe alogeničnih matičnih krvotvornih stanica [N-glycosylation of immunoglobulin G in chronic graft-versus-host disease]
Get PDFChronic graft-versus-host disease (cGvHD) is a systemic alloimmune and autoimmune disorder and the major late complication and leading cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation (alloHSCT). The disease is characterized by an altered homeostasis of the humoral immune response. Immunoglobulin G (IgG) glycoprotein is the main effector molecule of the humoral immune response. Changes in IgG glycosylation are associated with a number of autoimmune diseases.
IgG glycosylation analysis was done on two populations, American (213 cGvHD patients) and Croatian (30 cGvHD patients and 30 controls (after alloHSCT, without cGvHD)). The American population results showed significant correlation with cGvHD NIH joint/fascia and skin score, disease activity and intensity of systemic immunosuppression. ROC analysis confirmed that IgG glycosylation increases specificity and sensitivity of models using laboratory parameters and markers of inflammation. The Croatian logistic regression model built using glycan and laboratory parameters singled out glycopeptides for which it is justified to assume that they significantly contribute to the cGvHD discrimination.
This study has shown that IgG glycosylation plays a significant role in cGvHD pathology, and that further research could contribute to the understanding of the disease biology and lead to the necessary biomarker of chronic GVHD
Kardiomiopatije u djece - Današnja stajališta i naša iskustva Hrvatska retrospektivna epidemiološka studija 1988. - 2016. [Cardiomyopathies in children - Current opinions and our experiences Croatian retrospective epidemiological study 1988-2016]
Get PDFINTRODUCTION: Cardiomyopathies (CM) account for 3-5% of patients in the care of pediatric cardiologists.
They are found in all age groups, from fetal to adolescent age, and along with cardiology, teams from several
other pediatric subspecialties (neurology, metabolism, genetics) are also included. New findings have led to a
high survival rate. ----- GOAL: The primary goal is to present CM as an important part in the work of pediatric cardiologist
through an elaborate epidemiological study, current classifications, the latest diagnostic methods and treatments,
as well as the intertwining with other subspecialties. The secondary goal is to show that CM are no longer
“uncommon, insignificant and terminal”, but are common, significant and treatable diseases. ----- RESULTS: From January
1988 to December 2016 (28 years) in the Referral Center for Pediatric Cardiology, Department of Pediatrics,
Clinical Hospital Centre, 315 patients were diagnosed with cardiomyopathy,183 males (58.1%) and 132 females
(41.9%). In three different periods (10 , 12 and six years) a classification from 1996 was used (10). All three
periods have features of a population study, whereas the latter two also have features of an epidemiological study.
In all three periods there was a predominance of dilated cardiomyopathies (DCM) (42.5%) , followed by hypertrophic
cardiomyopathies (HCM) (37.1%) and restrictive cardiomyopathies (RCM) (6.7%) . Their relative relations
were in constant balance. A significant increase of some entity forms, arrhythmogenic right ventricular cardiomyopathies
(ARVCM) and non-compaction cardimyopathies (NCCM) has been observed, from 5.8% (1988-1998) to
16.2% (2010-2016). Owing to advances in diagnostic methods, number of unclassified CM has been decreasing significantly. The cause remained unknown in only 24.4% of DCM patients, and in 18.8% of HCM patients. In the
last 18 years the mortality rate of 7.4% (14/194) has been recorded, 50% (7/14) due to DCM. That is the result of
teamwork, targeted medical therapy, electrotherapy (electrical stimulation - ES, cardiac resynchronisation - CRS,
implantable cardioverter defibrilator - ICD) and surgical therapy (Morrow, pulmonary artery banding - PAB),
including heart transplantaton since 2011 (8 patients). Conclusion: Cardiomyopathies are after congenital heart
defects the most severe diseases under care of pediatric cardiologists. They require fluent teamwork of several
expert groups, and mastering of numerous diagnostic and therapeutic methods. Dilated cardiomyopathies are the
most common cause of death and the indication for heart transplatation in children
Analysis and quantification of bone healing after open wedge high tibial osteotomy
Get PDFBackground: The aim of this study was to analyze radiographic imaging techniques and to quantify bone ossification in the osteotomy gap after high tibial osteotomy. ------
Material and methods: Study phase 1: high tibial osteotomy was performed on six lower extremities of human body donors and experimental X‑rays and computed tomography (CT) scans were applied. Different techniques were evaluated by three specialists for best representation of the osteotomy gap. Study phase 2: optimized radiological techniques were used for follow-up on 12 patients. The radiographs were examined by 3 specialists measuring 10 different parameters. The CT scans were analyzed with semiautomatic computer software for quantification of bone ossification. -----
Results: The osteotomy gap was best represented in 30° of flexion in the knee and 20° internal rotation of the leg. There were significant changes of the medial width over time (p < 0.019) as well as of the length of fused osteotomy, the Schröter score, sclerosis, trabecular structure and zone area measurements. Sclerosis, medial width of the osteotomy and area measurements were detected as reproducible parameters. Bone mineral density was calculated using CT scans, showing a significantly higher value 12 weeks postoperatively (112.5 mg/cm3) than at baseline (54.6 mg/cm3). The ossification of the gap was visualized by color coding. -----
Conclusion: Sclerosis and medial width of the osteotomy gap as well as area measurements were determined as reproducible parameters for evaluation of bone healing. Quantification of bone ossification can be calculated with CT scans using a semiautomatic computer program and should be used for research in bone healing
