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Article ; Online: Periventricular hemorrhagic infarction in preterm neonates: Etiology and time of development.

Ilves, N / Metsvaht, T / Laugesaar, R / Rull, K / Lintrop, M / Laan, M / Loorits, D / Kool, P / Ilves, P

2024 Volume 17, Issue 1, Page(s) 111–121

Abstract: Background: To find the obstetrical and delivery associated risk factors of antenatal and postnatal grade III intraventricular hemorrhage (IVH) or periventricular hemorrhagic infarction (PVHI) in preterm neonates.: Methods: A retrospective study of ... ...

Abstract	Background: To find the obstetrical and delivery associated risk factors of antenatal and postnatal grade III intraventricular hemorrhage (IVH) or periventricular hemorrhagic infarction (PVHI) in preterm neonates. Methods: A retrospective study of obstetric and delivery associated risk factors included neonates (<35 gestational weeks) with severe IVH/PVHI (n = 120) and a prospectively collected control group (n = 50). The children were divided into: (1) antenatal onset group (n = 27) with insult visible on cerebral ultrasonography within the first 12 hours of birth or periventricular cystic changes visible in PVHI within the first 3 days; (2) neonatal onset group (n = 70) with insult diagnosed after initial normal findings or I-II grade IVH, and (3) unknown time-onset group (n = 23) with insult visible at > 12 h of age. Results: The mothers of the antenatal onset group had significantly more bacterial infections before delivery compared to the neonatal onset group: 20/27 (74.1%) versus 23/69 (33.3%), (odds ratio (OR) 5.7 [95% confidence interval 2.1-16]; p = 0.0008) or compared to the control group (11/50 (22%); OR 11 [2.8-42]; p = 0.0005). Placental histology revealed chorioamnionitis more often in the antenatal compared to the neonatal onset group (14/21 (66.7%) versus 16/42 (38.1%), respectively; OR 3.7 [1.18-11]; p = 0.025). Neonates with neonatal development of severe IVH/PVHI had significantly more complications during delivery or intensive care. Conclusions: Bacterial infection during pregnancy is an important risk factor for development of antenatal onset severe IVH or PVHI. In neonates born to mothers with severe bacterial infection during pregnancy, cerebral ultrasonography is indicated for early detection of severe IVH or PVHI.
MeSH term(s)	Infant, Newborn ; Child ; Female ; Humans ; Pregnancy ; Retrospective Studies ; Gestational Age ; Placenta/pathology ; Cerebral Hemorrhage/diagnostic imaging ; Cerebral Hemorrhage/epidemiology ; Cerebral Hemorrhage/etiology ; Infant, Newborn, Diseases ; Infarction/complications ; Infarction/pathology ; Bacterial Infections ; Infant, Premature, Diseases/diagnostic imaging ; Infant, Premature, Diseases/epidemiology ; Infant, Premature, Diseases/etiology
Language	English
Publishing date	2024-01-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2435387-5
ISSN	1878-4429 ; 1934-5798
ISSN (online)	1878-4429
ISSN	1934-5798
DOI	10.3233/NPM-230033
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Article: The thalamus and basal ganglia are smaller in children with epilepsy after perinatal stroke.

Vaher, Ulvi / Ilves, Norman / Ilves, Nigul / Laugesaar, Rael / Männamaa, Mairi / Loorits, Dagmar / Kool, Pille / Ilves, Pilvi

Frontiers in neurology

2023 Volume 14, Page(s) 1252472

Abstract: Background: Epilepsy is one of the most serious consequences of perinatal stroke. Epilepsy itself has been proposed as a risk factor for impaired cognitive, language, and behavioral functioning. It is still unclear which children develop epilepsy after ... ...

Abstract	Background: Epilepsy is one of the most serious consequences of perinatal stroke. Epilepsy itself has been proposed as a risk factor for impaired cognitive, language, and behavioral functioning. It is still unclear which children develop epilepsy after perinatal stroke. The current study aimed to evaluate the volume of the thalamus and the basal ganglia in children after perinatal stroke in relation to poststroke epilepsy. Methods: The follow-up study included 29 children with perinatal arterial ischemic stroke (AIS), 33 children with presumed periventricular venous infarction (PVI), and 46 age- and sex-matched healthy controls. Magnetic resonance imaging was performed in children between the ages of 4 and 18 years, and volumetric analysis by segmentation was used to evaluate the size of the thalamus, caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens. Results: During a median follow-up time of 12.8 years [interquartile range (IQR): 10.8-17.3] in the AIS group and 12.5 years (IQR: 9.3-14.8) in the PVI group ( Conclusion: In children with AIS, epilepsy or IED occurred more often compared to children with PVI. Both patients with AIS and PVI with severe damage to the basal ganglia and the thalamus have a higher risk of developing poststroke epilepsy and should be monitored more closely throughout childhood to initiate timely antiseizure medication and rehabilitation.
Language	English
Publishing date	2023-09-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2023.1252472
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Article ; Online: High Prevalence of Collagenopathies in Preterm- and Term-Born Children With Periventricular Venous Hemorrhagic Infarction.

Ilves, Norman / Pajusalu, Sander / Kahre, Tiina / Laugesaar, Rael / Šamarina, Ustina / Loorits, Dagmar / Kool, Pille / Ilves, Pilvi

Journal of child neurology

2023 Volume 38, Issue 6-7, Page(s) 373–388

Abstract: Introduction: The aim of this study was to evaluate genetic risk factors in term-born children with antenatal periventricular hemorrhagic infarction (PVHI), presumed antenatal periventricular venous infarction and periventricular hemorrhagic infarction ... ...

Abstract	Introduction: The aim of this study was to evaluate genetic risk factors in term-born children with antenatal periventricular hemorrhagic infarction (PVHI), presumed antenatal periventricular venous infarction and periventricular hemorrhagic infarction in preterm neonates. Methods: Genetic analysis and magnetic resonance imaging were performed in 85 children: term-born children (≥36 gestational weeks) with antenatal periventricular hemorrhagic infarction (n = 6) or presumed antenatal (n = 40) periventricular venous infarction and preterm children (<36 gestational weeks) with periventricular hemorrhagic infarction (n = 39). Genetic testing was performed using exome or large gene panel (n = 6700 genes) sequencing. Results: Pathogenic variants associated with stroke were found in 11 of 85 (12.9%) children with periventricular hemorrhagic infarction/periventricular venous infarction. Among the pathogenic variants, Conclusions: Children with periventricular hemorrhagic infarction/periventricular venous infarction have high prevalence of pathogenic variants in collagene genes (
MeSH term(s)	Infant, Newborn ; Humans ; Child ; Female ; Pregnancy ; Prevalence ; Cerebral Ventricles/pathology ; Stroke/pathology ; Developmental Disabilities/pathology ; Infarction/pathology
Language	English
Publishing date	2023-07-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639288-x
ISSN	1708-8283 ; 0883-0738
ISSN (online)	1708-8283
ISSN	0883-0738
DOI	10.1177/08830738231186233
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Article ; Online: The associations between the changes in serum inflammatory markers and bone mineral accrual in boys with overweight and obesity during pubertal maturation: a 3-year longitudinal study in Estonian boys.

Mengel, E / Tillmann, V / Remmel, L / Kool, P / Purge, P / Lätt, E / Jürimäe, J

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA

2018 Volume 29, Issue 9, Page(s) 2069–2078

Abstract: Adipose tissue produces different inflammatory cytokines which compromise bone mineral accrual during puberty. Vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), interleukin (IL)-8, and interferon-gamma (IFN-γ) are significantly ... ...

Abstract	Adipose tissue produces different inflammatory cytokines which compromise bone mineral accrual during puberty. Vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), interleukin (IL)-8, and interferon-gamma (IFN-γ) are significantly related to bone mineral accrual during pubertal maturation in boys with different BMI values. Introduction: This longitudinal study aims to identify the inflammatory markers that most strongly associate with pubertal bone mineral density (BMD) increment in boys with overweight and obesity (OWB). Methods: Twenty-six OWB and 29 normal-weight boys were followed yearly for 3 years to measure changes in 12 serum inflammatory markers, BMD (by DXA), and apparent volumetric BMD. The OWB group was further divided into two subgroups according to their BMI gain during the 3-year period. Data through time points presented as slopes were used to calculate correlation coefficients to explore the possible relationships between variables of interest. In the whole study group, linear mixed effects (LME) models were also used. Results: Increment in serum VEGF concentration was inversely associated with an increase in total body (TB) BMD (r = - 0.82, P = 0.02) and TB bone mineral content (BMC)/height (r = - 0.82, P = 0.02) in those OWB whose BMI gain was higher during pubertal years. In the whole study group, the LME model confirmed the inverse association between VEGF and TB BMC/height (P < 0.05). EGF was inversely associated with LS BMD and LS BMAD (P < 0.05), whereas there was a positive association between IL-8 and TB BMAD and between IFN-γ and LS BMD (P < 0.05). Conclusions: Lower increment in BMD in OWB with higher BMI gain is associated with increasing serum VEGF concentration during pubertal maturation. VEGF, EGF, IL-8, and IFN-γ are significantly associated with BMD during pubertal maturation in boys with different BMI values.
MeSH term(s)	Anthropometry/methods ; Biomarkers/blood ; Body Mass Index ; Child ; Cytokines/blood ; Epidermal Growth Factor/blood ; Humans ; Inflammation Mediators/metabolism ; Longitudinal Studies ; Male ; Obesity/blood ; Obesity/physiopathology ; Overweight/blood ; Overweight/physiopathology ; Puberty/blood ; Puberty/physiology ; Sexual Maturation/physiology ; Testosterone/blood ; Vascular Endothelial Growth Factor A/blood
Chemical Substances	Biomarkers ; Cytokines ; Inflammation Mediators ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Testosterone (3XMK78S47O) ; Epidermal Growth Factor (62229-50-9)
Language	English
Publishing date	2018-06-01
Publishing country	England
Document type	Journal Article
ZDB-ID	1064892-6
ISSN	1433-2965 ; 0937-941X
ISSN (online)	1433-2965
ISSN	0937-941X
DOI	10.1007/s00198-018-4580-z
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Article ; Online: Ipsilesional volume loss of basal ganglia and thalamus is associated with poor hand function after ischemic perinatal stroke.

Ilves, Nigul / Lõo, Silva / Ilves, Norman / Laugesaar, Rael / Loorits, Dagmar / Kool, Pille / Talvik, Tiina / Ilves, Pilvi

BMC neurology

2022 Volume 22, Issue 1, Page(s) 23

Abstract: Background: Perinatal stroke (PS) is the leading cause of hemiparetic cerebral palsy (CP). Involvement of the corticospinal tract on neonatal magnetic resonance imaging (MRI) is predictive of motor outcome in patients with hemiparetic CP. However, early ...

Abstract	Background: Perinatal stroke (PS) is the leading cause of hemiparetic cerebral palsy (CP). Involvement of the corticospinal tract on neonatal magnetic resonance imaging (MRI) is predictive of motor outcome in patients with hemiparetic CP. However, early MRI is not available in patients with delayed presentation of PS and prediction of hemiparesis severity remains a challenge. Aims: To evaluate the volumes of the basal ganglia, amygdala, thalamus, and hippocampus following perinatal ischemic stroke in relation to hand motor function in children with a history of PS and to compare the volumes of subcortical structures in children with PS and in healthy controls. Methods: Term born PS children with arterial ischemic stroke (AIS) (n = 16) and with periventricular venous infarction (PVI) (n = 18) were recruited from the Estonian Pediatric Stroke Database. MRI was accuired during childhood (4-18 years) and the volumes of the basal ganglia, thalamus, amygdala and hippocampus were calculated. The results of stroke patients were compared to the results of 42 age- and sex-matched healthy controls. Affected hand function was evaluated by Assisting Hand Assessment (AHA) and classified by the Manual Ability Classification System (MACS). Results: Compared to the control group, children with AIS had smaller volumes of the ipsi- and contralesional thalami, ipsilesional globus pallidus, nucleus accumbens and hippocampus (p < 0.005). Affected hand function in children with AIS was correlated with smaller ipsilesional thalamus, putamen, globus pallidus, hippocampus, amygdala and contralesional amygdala (r > 0.5; p < 0.05) and larger volume of the contralesional putamen and hippocampus (r < - 0.5; p < 0.05). In children with PVI, size of the ipsilesional caudate nucleus, globus pallidus, thalamus (p ≤ 0.001) and hippocampus (p < 0.03) was smaller compared to controls. Smaller volume of the ipsi- and contralesional thalami and ipsilesional caudate nucleus was correlated with affected hand function (r > 0.55; p < 0.05) in children with PVI. Conclusions: Smaller volume of ipsilesional thalamus was associated with poor affected hand function regardless of the perinatal stroke subtype. The pattern of correlation between hand function and volume differences in the other subcortical structures varied between children with PVI and AIS. Evaluation of subcortical structures is important in predicting motor outcome following perinatal stroke.
MeSH term(s)	Caudate Nucleus ; Child ; Female ; Hand ; Humans ; Infant, Newborn ; Magnetic Resonance Imaging ; Pregnancy ; Stroke/diagnostic imaging ; Thalamus/diagnostic imaging ; Upper Extremity
Language	English
Publishing date	2022-01-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2041347-6
ISSN	1471-2377 ; 1471-2377
ISSN (online)	1471-2377
ISSN	1471-2377
DOI	10.1186/s12883-022-02550-3
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Article ; Online: Language lateralization and outcome in perinatal stroke patients with different vascular types.

Ilves, Nigul / Männamaa, Mairi / Laugesaar, Rael / Ilves, Norman / Loorits, Dagmar / Vaher, Ulvi / Kool, Pille / Ilves, Pilvi

Brain and language

2022 Volume 228, Page(s) 105108

Abstract: Perinatal stroke affects child's language development and can change language lateralization. Language generation and comprehension tasks in functional magnetic resonance imaging were used to determine language lateralization in term born children with ... ...

Abstract	Perinatal stroke affects child's language development and can change language lateralization. Language generation and comprehension tasks in functional magnetic resonance imaging were used to determine language lateralization in term born children with perinatal left-side arterial ischemic stroke (AIS) (n = 9, mean age (SD) 13.4 (3.1) y.) and periventricular venous infarction (PVI) (n = 12, 11.8 (2.8) y.), and in healthy right-handed controls (n = 30, 11.6 (2.6) y.). Lateralization index was calculated for the Broca and Wernicke areas and correlated with language and cognitive outcomes measured by the Kaufman Assessment Battery for Children II ed. Language outcome in children with perinatal stroke is poorer compared to healthy controls. Children with small AIS lesions and most children with PVI showed left-side language activation. Most children with large AIS lesions and one child with large PVI had language activation reorganized to the right hemisphere. Language reorganization to the unlesioned right hemisphere did not ensure normal language outcome.
MeSH term(s)	Child ; Female ; Hand ; Humans ; Language ; Magnetic Resonance Imaging/methods ; Pregnancy ; Stroke/complications ; Stroke/diagnostic imaging ; Wernicke Area
Language	English
Publishing date	2022-03-22
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	7448-2
ISSN	1090-2155 ; 0093-934X
ISSN (online)	1090-2155
ISSN	0093-934X
DOI	10.1016/j.bandl.2022.105108
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Article ; Online: Maternal Pyelonephritis as a Potential Cause of Perinatal Periventricular Venous Infarction in Term-Born Children.

Ilves, Norman / Laugesaar, Rael / Rull, Kristiina / Metsvaht, Tuuli / Lintrop, Mare / Laan, Maris / Loorits, Dagmar / Kool, Pille / Ilves, Pilvi

Journal of child neurology

2022 Volume 37, Issue 8-9, Page(s) 677–688

Abstract: Introduction: ...

Abstract	Introduction:
MeSH term(s)	Child ; Female ; Humans ; Infant, Newborn ; Infarction/epidemiology ; Infarction/etiology ; Pregnancy ; Prospective Studies ; Pyelonephritis/complications ; Pyelonephritis/epidemiology ; Retrospective Studies ; Risk Factors
Language	English
Publishing date	2022-07-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639288-x
ISSN	1708-8283 ; 0883-0738
ISSN (online)	1708-8283
ISSN	0883-0738
DOI	10.1177/08830738221109340
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Article ; Online: Early postnatal growth in children with HLA-conferred susceptibility to type 1 diabetes.

Peet, A / Hämäläinen, A-M / Kool, P / Ilonen, J / Knip, M / Tillmann, V

Diabetes/metabolism research and reviews

2014 Volume 30, Issue 1, Page(s) 60–68

Abstract: Aims/hypothesis: An association between increased length/height and weight gain and risk of type 1 diabetes (T1D) has been reported in children. We set out to investigate the potential contribution of T1D human leukocyte antigen (HLA) risk genotypes to ... ...

Abstract	Aims/hypothesis: An association between increased length/height and weight gain and risk of type 1 diabetes (T1D) has been reported in children. We set out to investigate the potential contribution of T1D human leukocyte antigen (HLA) risk genotypes to this association in two countries with a contrasting disease incidence. Methods: In Estonia and Finland, length and weight were monitored up to the age of 24 months in 688 subjects. According to their HLA genotypes, the children were divided into four groups, those with very high, high or moderate risk for T1D, as well as a neutral/control group. Relative length and weight (SDS) were assessed and compared at 3, 6, 12, 18 and 24 months using World Health Organization (WHO) growth curves. Results: The mean relative length at the age of 24 months was lower in the group with the very high risk HLA genotype compared to the controls (p < 0.05). The mean relative weight differed between those two groups at the age of 12, 18 and 24 months (p < 0.05). When Estonian and Finnish cohorts were analyzed separately, the relative length showed similar but non-significant trends in both countries, while in Estonia the changes in weight at some time points still remained significant (p < 0.05). Conclusions: Children with the highest HLA-conferred risk for T1D gained less weight and length during the first 24 months of life, and this feature was more pronounced in the Estonian children.
MeSH term(s)	Body Height ; Body Weight ; Child, Preschool ; Diabetes Mellitus, Type 1/genetics ; Disease Susceptibility/immunology ; Estonia ; European Continental Ancestry Group ; Female ; Finland ; Genetic Predisposition to Disease ; Genotype ; Growth and Development/genetics ; Growth and Development/immunology ; HLA Antigens/genetics ; Humans ; Infant ; Insulin Resistance/genetics ; Male ; Sex Characteristics
Chemical Substances	HLA Antigens
Language	English
Publishing date	2014-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1470192-3
ISSN	1520-7560 ; 1520-7552
ISSN (online)	1520-7560
ISSN	1520-7552
DOI	10.1002/dmrr.2449
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Article ; Online: Extensive BMI Gain in Puberty is Associated with Lower Increments in Bone Mineral Density in Estonian Boys with Overweight and Obesity: A 3-Year Longitudinal Study.

Mengel, Eva / Tillmann, Vallo / Remmel, Liina / Kool, Pille / Purge, Priit / Lätt, Evelin / Jürimäe, Jaak

Calcified tissue international

2017 Volume 101, Issue 2, Page(s) 174–181

Abstract: The aim of this 3-year prospective study was to examine changes in bone mineral characteristics during pubertal maturation in boys with different BMI values at the beginning of puberty and with different BMI increments during puberty. 26 boys with ... ...

Abstract	The aim of this 3-year prospective study was to examine changes in bone mineral characteristics during pubertal maturation in boys with different BMI values at the beginning of puberty and with different BMI increments during puberty. 26 boys with overweight and obesity (OWB) and 29 normal weight boys (NWB) were studied yearly for 3 years from the age of 11 years to measure the changes in different bone mineral characteristics. The OWB group was further divided into two subgroups according to extensive or non-extensive BMI increment during 3-year period. OWB had higher (P < 0.01) baseline total body (TB) bone mineral density (BMD), TB bone mineral content (BMC), TB BMC for height, lumbar spine (LS) BMD, and LS BMC compared to NWB. Throughout the study period, OWB gained more TB BMD (P = 0.0001), TB BMC (P = 0.0048), TB BMC for height (P = 0.0124), LS BMD (P = 0.0029), and LS BMC (P = 0.0022) compared to NWB. Also during the study period, TB BMD (P = 0.0065), TB BMC (P = 0.0141), TB BMC for height (P = 0.0199), LS BMD (P = 0.0066), LS apparent volumetric BMD (BMAD) (P = 0.0075), and LS BMC (P = 0.017) increased significantly less in those OWB whose BMI increased more extensively. Extensive BMI gain is associated with lower increments in bone mineral characteristics in boys with overweight and obesity. Unfavorable increment in total body fat mass and percentage during pubertal years could be one reason for that.
Language	English
Publishing date	2017-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	304266-2
ISSN	1432-0827 ; 0944-0747 ; 0008-0594 ; 0171-967X
ISSN (online)	1432-0827
ISSN	0944-0747 ; 0008-0594 ; 0171-967X
DOI	10.1007/s00223-017-0273-4
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Article ; Online: Changes in inflammatory markers in estonian pubertal boys with different BMI values and increments: A 3-Year Follow-Up Study.

Mengel, Eva / Tillmann, Vallo / Remmel, Liina / Kool, Pille / Purge, Priit / Lätt, Evelin / Jürimäe, Jaak

Obesity (Silver Spring, Md.)

2017 Volume 25, Issue 3, Page(s) 600–607

Abstract: Objective: Serum inflammatory markers could help to identify those boys with overweight (OWB) who gain weight more extensively during puberty. This study aimed to examine the longitudinal changes in different serum inflammatory markers through puberty ... ...

Abstract	Objective: Serum inflammatory markers could help to identify those boys with overweight (OWB) who gain weight more extensively during puberty. This study aimed to examine the longitudinal changes in different serum inflammatory markers through puberty in boys with different BMI values and increments. Methods: Twenty-six OWB and 29 normal-weight boys (NWB) were followed yearly for 3 years to measure changes in BMI and serum concentrations of 12 inflammatory markers. Results: OWB had higher (P < 0.033) baseline interleukin (IL)-6, IL-8, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-1α concentrations in comparison with NWB. Over the 3-year period, IFN-γ (P = 0.0001) and TNF-α (P = 0.0042) decreased more in OWB compared to NWB. Serum IL-8, monocyte chemoattractant protein (MCP)-1, and leptin increased further in those OWB who gained BMI more extensively through puberty compared to OWB who gained weight at slower rates (P < 0.033). Conclusions: Serum IFN-γ and TNF-α levels decreased more during pubertal years in OWB compared to NWB, indicating that pubertal maturation itself may have a favorable impact on the inflammation of obesity. Serum IL-8, MCP-1, and leptin could help to identify OWB who gain BMI more extensively during pubertal years.
MeSH term(s)	Adolescent ; Biomarkers/blood ; Body Mass Index ; Chemokine CCL2/blood ; Estonia ; Follow-Up Studies ; Humans ; Interferon-gamma/blood ; Interleukin-1alpha/blood ; Interleukin-6/blood ; Interleukin-8/blood ; Leptin/blood ; Male ; Overweight/blood ; Puberty/blood ; Tumor Necrosis Factor-alpha/blood
Chemical Substances	Biomarkers ; CCL2 protein, human ; Chemokine CCL2 ; IL6 protein, human ; Interleukin-1alpha ; Interleukin-6 ; Interleukin-8 ; Leptin ; Tumor Necrosis Factor-alpha ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2017-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2230457-5
ISSN	1930-739X ; 1071-7323 ; 1930-7381
ISSN (online)	1930-739X
ISSN	1071-7323 ; 1930-7381
DOI	10.1002/oby.21756
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