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Selective serotonin reuptake inhibitors (SSRIs) are widely used for treating neuropsychiatric disorders. However, the exact mechanism of action and why effects can take several weeks to manifest is not clear. The hypothesis of neuroplasticity is supported by preclinical studies, but the evidence in humans is limited. Here, we investigate the effects of the SSRI escitalopram on presynaptic density as a proxy for synaptic plasticity. In a double-blind placebo-controlled study (NCT04239339), 32 healthy participants with no history of psychiatric or cognitive disorders were randomized to receive daily oral dosing of either 20 mg escitalopram (n = 17) or a placebo (n = 15). After an intervention period of 3–5 weeks, participants underwent a [11C]UCB-J PET scan (29 with full arterial input function) to quantify synaptic vesicle glycoprotein 2A (SV2A) density in the hippocampus and the neocortex. Whereas we find no statistically significant group difference in SV2A binding after an average of 29 (range: 24–38) days of intervention, our secondary analyses show a time-dependent effect of escitalopram on cerebral SV2A binding with positive associations between [11C]UCB-J binding and duration of escitalopram intervention. Our findings suggest that brain synaptic plasticity evolves over 3–5 weeks in healthy humans following daily intake of escitalopram. This is the first in vivo evidence to support the hypothesis of neuroplasticity as a mechanism of action for SSRIs in humans and it offers a plausible biological explanation for the delayed treatment response commonly observed in patients treated with SSRIs. While replication is warranted, these results have important implications for the design of future clinical studies investigating the neurobiological effects of SSRIs., Selective serotonin reuptake inhibitors (SSRIs) are widely used for treating neuropsychiatric disorders. However, the exact mechanism of action and why effects can take several weeks to manifest is not clear. The hypothesis of neuroplasticity is supported by preclinical studies, but the evidence in humans is limited. Here, we investigate the effects of the SSRI escitalopram on presynaptic density as a proxy for synaptic plasticity. In a double-blind placebo-controlled study (NCT04239339), 32 healthy participants with no history of psychiatric or cognitive disorders were randomized to receive daily oral dosing of either 20 mg escitalopram (n = 17) or a placebo (n = 15). After an intervention period of 3-5 weeks, participants underwent a [11C]UCB-J PET scan (29 with full arterial input function) to quantify synaptic vesicle glycoprotein 2A (SV2A) density in the hippocampus and the neocortex. Whereas we find no statistically significant group difference in SV2A binding after an average of 29 (range: 24-38) days of intervention, our secondary analyses show a time-dependent effect of escitalopram on cerebral SV2A binding with positive associations between [11C]UCB-J binding and duration of escitalopram intervention. Our findings suggest that brain synaptic plasticity evolves over 3-5 weeks in healthy humans following daily intake of escitalopram. This is the first in vivo evidence to support the hypothesis of neuroplasticity as a mechanism of action for SSRIs in humans and it offers a plausible biological explanation for the delayed treatment response commonly observed in patients treated with SSRIs. While replication is warranted, these results have important implications for the design of future clinical studies investigating the neurobiological effects of SSRIs.

Selective serotonin reuptake inhibitors (SSRIs) are widely used for treating neuropsychiatric disorders. However, the exact mechanism of action and why effects can take several weeks to manifest is not clear. The hypothesis of neuroplasticity is supported by preclinical studies, but the evidence in humans is limited. Here, we investigate the effects of the SSRI escitalopram on presynaptic density as a proxy for synaptic plasticity. In a double-blind placebo-controlled study (NCT04239339), 32 healthy participants with no history of psychiatric or cognitive disorders were randomized to receive daily oral dosing of either 20 mg escitalopram (n = 17) or a placebo (n = 15). After an intervention period of 3–5 weeks, participants underwent a [11C]UCB-J PET scan (29 with full arterial input function) to quantify synaptic vesicle glycoprotein 2A (SV2A) density in the hippocampus and the neocortex. Whereas we find no statistically significant group difference in SV2A binding after an average of 29 (range: 24–38) days of intervention, our secondary analyses show a time-dependent effect of escitalopram on cerebral SV2A binding with positive associations between [11C]UCB-J binding and duration of escitalopram intervention. Our findings suggest that brain synaptic plasticity evolves over 3–5 weeks in healthy humans following daily intake of escitalopram. This is the first in vivo evidence to support the hypothesis of neuroplasticity as a mechanism of action for SSRIs in humans and it offers a plausible biological explanation for the delayed treatment response commonly observed in patients treated with SSRIs. While replication is warranted, these results have important implications for the design of future clinical studies investigating the neurobiological effects of SSRIs., Selective serotonin reuptake inhibitors (SSRIs) are widely used for treating neuropsychiatric disorders. However, the exact mechanism of action and why effects can take several weeks to manifest is not clear. The hypothesis of neuroplasticity is supported by preclinical studies, but the evidence in humans is limited. Here, we investigate the effects of the SSRI escitalopram on presynaptic density as a proxy for synaptic plasticity. In a double-blind placebo-controlled study (NCT04239339), 32 healthy participants with no history of psychiatric or cognitive disorders were randomized to receive daily oral dosing of either 20 mg escitalopram (n = 17) or a placebo (n = 15). After an intervention period of 3-5 weeks, participants underwent a [11C]UCB-J PET scan (29 with full arterial input function) to quantify synaptic vesicle glycoprotein 2A (SV2A) density in the hippocampus and the neocortex. Whereas we find no statistically significant group difference in SV2A binding after an average of 29 (range: 24-38) days of intervention, our secondary analyses show a time-dependent effect of escitalopram on cerebral SV2A binding with positive associations between [11C]UCB-J binding and duration of escitalopram intervention. Our findings suggest that brain synaptic plasticity evolves over 3-5 weeks in healthy humans following daily intake of escitalopram. This is the first in vivo evidence to support the hypothesis of neuroplasticity as a mechanism of action for SSRIs in humans and it offers a plausible biological explanation for the delayed treatment response commonly observed in patients treated with SSRIs. While replication is warranted, these results have important implications for the design of future clinical studies investigating the neurobiological effects of SSRIs.

In Denmark, a nationwide COVID-19 lockdown was implemented on March 12, 2020 and eased on April 14, 2020. The COVID-19 lockdown featured reduced prevalence of extremely preterm or extremely low birthweight births. This study aims to explore the impact of this COVID-19 lockdown on term birthweights in Denmark. We conducted a nationwide register-based cohort study on 27,870 live singleton infants, born at term (weeks 37-41), between March 12 and April 14, 2015-2020, using data from the Danish Neonatal Screening Biobank. Primary outcomes, corrected for confounders, were birthweight, small-for-gestational-age (SGA), and large-for-gestational-age (LGA), comparing the COVID-19 lockdown to the previous five years. Data were analysed using linear regression to assess associations with birthweight. Multinomial logistic regression was used to assess associations with relative-size-for-gestational-age (xGA) categories. Adjusted mean birthweight was significantly increased by 16.9 g (95% CI = 4.1-31.3) during the lockdown period. A dip in mean birthweight was found in gestational weeks 37 and 38 balanced by an increase in weeks 40 and 41. The 2020 lockdown period was associated with an increased LGA prevalence (aOR 1.13, 95% CI = 1.05-1.21). No significant changes in proportions of xGA groups were found between 2015 and 2019. The nationwide COVID-19 lockdown resulted in a small but significant increase in birthweight and proportion of LGA infants, driven by an increase in birthweight in gestational weeks 40 and 41.

Objective To evaluate the association between maternal obesity and congenital heart defects (CHDs) in the offspring when including live births, stillbirths and terminated pregnancies and to investigate if interpregnancy weight change between the first and second pregnancy influences risk of fetal CHDs. Methods A nationwide cohort study of all singleton pregnancies in Denmark from 2008 to 2018. All data on maternal and offspring characteristics were retrieved from the Danish Fetal Medicine Database including prenatal diagnoses. CHDs and severe CHDs were defined according to European Surveillance of Congenital Anomalies’ definitions. Children or fetuses with chromosomal aberrations were excluded. Relative risks (RRs) were calculated using log-linear Poisson models. Results Of the 547 178 pregnancies included in the cohort, 5 498 had CHDs (1.00%). Risk of CHDs became gradually higher with higher maternal body mass index (BMI); for BMI 30-34.9, adjusted relative risk (aRR) = 1.23, 95% confidence interval (CI) 1.12-1.36, for BMI 35-39.9, aRR = 1.26, 95% CI 1.09-1.46 and for BMI ≥ 40, aRR = 1.81, 95% CI 1.50-2.15. Data was adjusted for maternal age, smoking status and birth year. The same pattern was seen for the subgroup of severe CHDs. Among the atrioventricular septal defects (n = 245), a particularly strong association with maternal BMI ≥ 40 was seen, aRR = 4.19, 95% CI 2.13-7.42. Interpregnancy BMI change was positively, albeit not significanty, associated with risk of CHDs in the second pregnancy when adjusting for maternal age and BMI, with an aRR = 1.27, 95% CI 0.96-1.64 among persons with a BMI increase of ≥ 4 kg/m2 was found. Conclusion When including both pre-and post-natally diagnosed CHDs, this study showed a dose-response association between maternal BMI and risk of CHDs in the offspring. However, only a non-significant trend was seen between interpregnancy BMI changes and risk of CHDs., Objective To evaluate the association between maternal obesity and congenital heart defects (CHDs) in the offspring when including live births, stillbirths and terminated pregnancies and to investigate if interpregnancy weight change between the first and second pregnancy influences risk of fetal CHDs. Methods A nationwide cohort study of all singleton pregnancies in Denmark from 2008 to 2018. All data on maternal and offspring characteristics were retrieved from the Danish Fetal Medicine Database including prenatal diagnoses. CHDs and severe CHDs were defined according to European Surveillance of Congenital Anomalies’ definitions. Children or fetuses with chromosomal aberrations were excluded. Relative risks (RRs) were calculated using log-linear Poisson models. Results Of the 547 178 pregnancies included in the cohort, 5 498 had CHDs (1.00%). Risk of CHDs became gradually higher with higher maternal body mass index (BMI); for BMI 30-34.9, adjusted relative risk (aRR) = 1.23, 95% confidence interval (CI) 1.12-1.36, for BMI 35-39.9, aRR = 1.26, 95% CI 1.09-1.46 and for BMI ≥ 40, aRR = 1.81, 95% CI 1.50-2.15. Data was adjusted for maternal age, smoking status and birth year. The same pattern was seen for the subgroup of severe CHDs. Among the atrioventricular septal defects (n = 245), a particularly strong association with maternal BMI ≥ 40 was seen, aRR = 4.19, 95% CI 2.13-7.42. Interpregnancy BMI change was positively, albeit not significanty, associated with risk of CHDs in the second pregnancy when adjusting for maternal age and BMI, with an aRR = 1.27, 95% CI 0.96-1.64 among persons with a BMI increase of ≥ 4 kg/m2 was found. Conclusion When including both pre-and post-natally diagnosed CHDs, this study showed a dose-response association between maternal BMI and risk of CHDs in the offspring. However, only a non-significant trend was seen between interpregnancy BMI changes and risk of CHDs.

In Denmark, a nationwide COVID-19 lockdown was implemented on March 12, 2020 and eased on April 14, 2020. The COVID-19 lockdown featured reduced prevalence of extremely preterm or extremely low birthweight births. This study aims to explore the impact of this COVID-19 lockdown on term birthweights in Denmark. We conducted a nationwide register-based cohort study on 27,870 live singleton infants, born at term (weeks 37-41), between March 12 and April 14, 2015-2020, using data from the Danish Neonatal Screening Biobank. Primary outcomes, corrected for confounders, were birthweight, small-for-gestational-age (SGA), and large-for-gestational-age (LGA), comparing the COVID-19 lockdown to the previous five years. Data were analysed using linear regression to assess associations with birthweight. Multinomial logistic regression was used to assess associations with relative-size-for-gestational-age (xGA) categories. Adjusted mean birthweight was significantly increased by 16.9 g (95% CI = 4.1-31.3) during the lockdown period. A dip in mean birthweight was found in gestational weeks 37 and 38 balanced by an increase in weeks 40 and 41. The 2020 lockdown period was associated with an increased LGA prevalence (aOR 1.13, 95% CI = 1.05-1.21). No significant changes in proportions of xGA groups were found between 2015 and 2019. The nationwide COVID-19 lockdown resulted in a small but significant increase in birthweight and proportion of LGA infants, driven by an increase in birthweight in gestational weeks 40 and 41.

In dogs, the use of probiotics for preventive or therapeutic purposes has become increasingly common, however the evidence for beneficial effects are often limited. The aim of this study was to investigate the effects of feeding a diet containing Enterococcus faecium NCIMB 10415 on faecal quality, faecal short-chain fatty acid concentrations, serum concentrations of cholesterol, triglycerides, cobalamin and folate as well as faecal microbiome in adult dogs. Eleven healthy client owned dogs were enrolled in a randomized, double-blinded crossover study. All dogs were fed the same balanced diet with or without incorporation of Enterococcus faecium NCIMB 10415 for 16 days each. Blood and faecal samples were collected at baseline and during the feeding trial and owners recorded daily faecal scores. An Enterococcus spp. ASV, likely representing E. faecium NCIMB 10415 was detected in the faecal microbiome of some dogs 18–19 days after withdrawal of oral supplementation. Inclusion of E. faecium decreased circulating cholesterol (p = 0.008) compared to baseline. There were no differences in cholesterol concentrations between diets. Owners reported 0.6 ± 0.3) days less of loose stools compared to the control diet. Comparing to baseline, both diets significantly increased faecal concentration of acetate and butyrate, decreased serum cobalamin and increased faecal microbial diversity. Decreased serum cobalamin, and increased faecal acetate correlated with decreases in the Fusobacterium, Streptococcus, Blautia, and Peptoclostridium. Except for effects on circulating cholesterol and faecal score, effects were observed regardless of the addition of E. faecium. It is therefore likely that these effects can be contributed to dietary prebiotic effects on the faecal microbiome.

In dogs, the use of probiotics for preventive or therapeutic purposes has become increasingly common, however the evidence for beneficial effects are often limited. The aim of this study was to investigate the effects of feeding a diet containing Enterococcus faecium NCIMB 10415 on faecal quality, faecal short-chain fatty acid concentrations, serum concentrations of cholesterol, triglycerides, cobalamin and folate as well as faecal microbiome in adult dogs. Eleven healthy client owned dogs were enrolled in a randomized, double-blinded crossover study. All dogs were fed the same balanced diet with or without incorporation of Enterococcus faecium NCIMB 10415 for 16 days each. Blood and faecal samples were collected at baseline and during the feeding trial and owners recorded daily faecal scores. An Enterococcus spp. ASV, likely representing E. faecium NCIMB 10415 was detected in the faecal microbiome of some dogs 18–19 days after withdrawal of oral supplementation. Inclusion of E. faecium decreased circulating cholesterol (p = 0.008) compared to baseline. There were no differences in cholesterol concentrations between diets. Owners reported 0.6 ± 0.3) days less of loose stools compared to the control diet. Comparing to baseline, both diets significantly increased faecal concentration of acetate and butyrate, decreased serum cobalamin and increased faecal microbial diversity. Decreased serum cobalamin, and increased faecal acetate correlated with decreases in the Fusobacterium, Streptococcus, Blautia, and Peptoclostridium. Except for effects on circulating cholesterol and faecal score, effects were observed regardless of the addition of E. faecium. It is therefore likely that these effects can be contributed to dietary prebiotic effects on the faecal microbiome.

Acquired canine proximal renal tubulopathy (Fanconi syndrome) related to excessive ingestion of jerky treats has been recognized since 2007. This study aimed to improve knowledge about the syndrome’s characteristics, especially long-term outcome. By reaching out to veterinarians and dog owners, dogs suspected of jerky induced Fanconi syndrome were identified. The dog’s medical records were reviewed, and owners interviewed. Data was analyzed using linear mixed models (p < 0.05 was considered statistically significant) and descriptive statistics are reported. Thirty dogs, median body weight 6.8 (range 1.2–59) kg and age 6.5 (0.5–14) years, were enrolled as suspected cases based on history of jerkey ingestion and confirmed normoglycemic/hypoglycemic glycosuria. Clinical signs included polydipsia (23/30), polyuria (21/30), lethargy (19/30), weight loss (15/30), hyporexia (11/30), vomiting (7/30), diarrhea (7/30) and no clinical signs (2/30). Para-clinical findings included azotemia (6/28), hypophosphatemia (9/25), metabolic acidosis (3/8), hypokalemia (6/20), proteinuria (13/26), aminoaciduria (4/4), hematuria (22/29) and ketonuria (7/27). Clinical signs resolved in 22/28 within 11 (0.3–52) weeks and glycosuria resolved in 28/30 within 6.5 (1–31) weeks. There were no associations between serum creatinine and urea and the amount/duration of jerky ingestion. Serum symmetric dimethylarginine concentrations were only available for a few dogs, therefore no conclusion was achieved on a possible association with duration of jerky ingestion. Apart from a larger percentage of dogs achieving complete recovery, the current findings are in agreement with previous reports.

Acquired canine proximal renal tubulopathy (Fanconi syndrome) related to excessive ingestion of jerky treats has been recognized since 2007. This study aimed to improve knowledge about the syndrome’s characteristics, especially long-term outcome. By reaching out to veterinarians and dog owners, dogs suspected of jerky induced Fanconi syndrome were identified. The dog’s medical records were reviewed, and owners interviewed. Data was analyzed using linear mixed models (p < 0.05 was considered statistically significant) and descriptive statistics are reported. Thirty dogs, median body weight 6.8 (range 1.2–59) kg and age 6.5 (0.5–14) years, were enrolled as suspected cases based on history of jerkey ingestion and confirmed normoglycemic/hypoglycemic glycosuria. Clinical signs included polydipsia (23/30), polyuria (21/30), lethargy (19/30), weight loss (15/30), hyporexia (11/30), vomiting (7/30), diarrhea (7/30) and no clinical signs (2/30). Para-clinical findings included azotemia (6/28), hypophosphatemia (9/25), metabolic acidosis (3/8), hypokalemia (6/20), proteinuria (13/26), aminoaciduria (4/4), hematuria (22/29) and ketonuria (7/27). Clinical signs resolved in 22/28 within 11 (0.3–52) weeks and glycosuria resolved in 28/30 within 6.5 (1–31) weeks. There were no associations between serum creatinine and urea and the amount/duration of jerky ingestion. Serum symmetric dimethylarginine concentrations were only available for a few dogs, therefore no conclusion was achieved on a possible association with duration of jerky ingestion. Apart from a larger percentage of dogs achieving complete recovery, the current findings are in agreement with previous reports.

Pretargeted imaging can be used to visualize and quantify slow-accumulating targeting vectors with short-lived radionuclides such as fluorine-18 - the most popular clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-lived radionuclides. Currently, the tetrazine ligation is the most popular bioorthogonal reaction for pretargeted imaging, but a direct18F-labeling strategy for highly reactive tetrazines, which would be highly beneficial if not essential for clinical translation, has thus far not been reported. In this work, a simple, scalable and reliable direct18F-labeling procedure has been developed. We initially studied the applicability of different leaving groups and labeling methods to develop this procedure. The copper-mediated18F-labeling exploiting stannane precursors showed the most promising results. This approach was then successfully applied to a set of tetrazines, including highly reactive H-tetrazines, suitable for pretargeted PET imaging. The labeling succeeded in radiochemical yields (RCYs) of up to approx. 25%. The new procedure was then applied to develop a pretargeting tetrazine-based imaging agent. The tracer was synthesized in a satisfactory RCY ofca.10%, with a molar activity of 134 ± 22 GBq μmol−1and a radiochemical purity of >99%. Further evaluation showed that the tracer displayed favorable characteristics (target-to-background ratios and clearance) that may qualify it for future clinical translation.

Background Congenital heart defects (CHDs) are the most common congenital malformations. The aetiology of CHDs is complex. Large cohort studies and systematic reviews and meta-analyses based on these have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hypertension, and preeclampsia, all conditions that can be related to insulin resistance or hyperglycaemia. However, the clinical reality is that these conditions often occur simultaneously. The aim of this review is, in consequence, both to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia and CHDs in the offspring, as well as the significance of combinations, such as metabolic syndrome, as risk factors. Methods A systematic literature search of papers published between January 1, 1990 and January 14, 2021 was conducted using PubMed and Embase. Studies were eligible if they were published in English and were case-control or cohort studies. The exposures of interest were maternal overweight or obesity, hypertension, preeclampsia, diabetes, dyslipidaemia, and/or metabolic syndrome, and the outcome of interest was CHDs in the offspring. Furthermore, the studies were included according to a quality assessment score. Results Of the 2,250 identified studies, 32 qualified for inclusion. All but one study investigated only the individual metabolic disorders. Some disorders (obesity, gestational diabetes, and hypertension) increased risk of CHDs marginally whereas pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs, without consistent differences between CHD subtypes. A single study suggested a possible additive effect of maternal obesity and gestational diabetes. Conclusions Future studies of the role of aberrations of the glucose-insulin homeostasis in the common aetiology and mechanism

Leptin is secreted by the placenta and has a multi-facetted role in the regulation of functions related to pregnancy. Metabolic disorders and insufficient homeostatic compensatory mechanisms involving leptin during pregnancy play a decisive role in the development of pre-eclampsia (PE) and give rise to compromised intrauterine growth conditions and aberrant birth weight of offspring. This review was compiled to elucidate the metabolic background of PE and its relationship with adverse intrauterine growth conditions through the examination of leptin as well as to describe possible mechanisms linking leptin to fetal growth restriction. This review illustrates that leptin in PE is dysregulated in maternal, fetal, and placental compartments. There is no single set of unifying mechanisms within the spectrum of PE, and regulatory mechanisms involving leptin are specific to each situation. We conclude that dysregulated leptin is involved in fetal growth at many levels through complex interactions with parallel pregnancy systems and probably throughout the entirety of pregnancy.

Background Congenital heart defects (CHDs) are the most common congenital malformations. The aetiology of CHDs is complex. Large cohort studies and systematic reviews and meta-analyses based on these have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hypertension, and preeclampsia, all conditions that can be related to insulin resistance or hyperglycaemia. However, the clinical reality is that these conditions often occur simultaneously. The aim of this review is, in consequence, both to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia and CHDs in the offspring, as well as the significance of combinations, such as metabolic syndrome, as risk factors. Methods A systematic literature search of papers published between January 1, 1990 and January 14, 2021 was conducted using PubMed and Embase. Studies were eligible if they were published in English and were case-control or cohort studies. The exposures of interest were maternal overweight or obesity, hypertension, preeclampsia, diabetes, dyslipidaemia, and/or metabolic syndrome, and the outcome of interest was CHDs in the offspring. Furthermore, the studies were included according to a quality assessment score. Results Of the 2,250 identified studies, 32 qualified for inclusion. All but one study investigated only the individual metabolic disorders. Some disorders (obesity, gestational diabetes, and hypertension) increased risk of CHDs marginally whereas pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs, without consistent differences between CHD subtypes. A single study suggested a possible additive effect of maternal obesity and gestational diabetes. Conclusions Future studies of the role of aberrations of the glucose-insulin homeostasis in the common aetiology and mechanism

Leptin is secreted by the placenta and has a multi-facetted role in the regulation of functions related to pregnancy. Metabolic disorders and insufficient homeostatic compensatory mechanisms involving leptin during pregnancy play a decisive role in the development of pre-eclampsia (PE) and give rise to compromised intrauterine growth conditions and aberrant birth weight of offspring. This review was compiled to elucidate the metabolic background of PE and its relationship with adverse intrauterine growth conditions through the examination of leptin as well as to describe possible mechanisms linking leptin to fetal growth restriction. This review illustrates that leptin in PE is dysregulated in maternal, fetal, and placental compartments. There is no single set of unifying mechanisms within the spectrum of PE, and regulatory mechanisms involving leptin are specific to each situation. We conclude that dysregulated leptin is involved in fetal growth at many levels through complex interactions with parallel pregnancy systems and probably throughout the entirety of pregnancy.

Background: Specific biomarkers of pyelonephritis (PN) in cats are lacking. MicroRNAs (miRNAs) have diagnostic potential in human nephropathies. Objectives: To investigate the presence/stability of miRNAs in whole urine of cats and the discriminatory potential of selected urinary miRNAs for PN in cats. Animals: Twelve healthy cats, 5 cats with PN, and 13 cats with chronic kidney disease (n = 5), subclinical bacteriuria (n = 3), and ureteral obstructions (n = 5) recruited from 2 companion animal hospitals. Methods: Prospective case-control study. Expression profiles of 24 miRNAs were performed by quantitative PCR (qPCR). Effect of storage temperature (4°C [24 hours], −20°C, and −80°C) was determined for a subset of miRNAs in healthy cats. Results: Urinary miR-4286, miR-30c, miR-204, miR4454, miR-21, miR-16, miR-191, and miR-30a were detected. For the majority of miRNAs tested, storage at 4°C and −20°C resulted in significantly lower miRNA yield compared to storage at −80°C (mean log2fold changes across miRNAs from −0.5 ± 0.4 SD to −1.20 ± 0.4 SD (4°C versus −80°C) and from −0.7 ± 0.2 SD to −1.20 ± 0.3 SD (−20°C versus −80°C)). Cats with PN had significantly upregulated miR-16 with a mean log2fold change of 1.0 ± 0.4 SD, compared with controls (−0.1 ± 0.2, P =.01) and other urological conditions (0.6 ± 0.3, P =.04). Conclusions: Upregulation of miR16 might be PN-specific, pathogen-specific (Escherichia coli), or both.

Background: Specific biomarkers of pyelonephritis (PN) in cats are lacking. MicroRNAs (miRNAs) have diagnostic potential in human nephropathies. Objectives: To investigate the presence/stability of miRNAs in whole urine of cats and the discriminatory potential of selected urinary miRNAs for PN in cats. Animals: Twelve healthy cats, 5 cats with PN, and 13 cats with chronic kidney disease (n = 5), subclinical bacteriuria (n = 3), and ureteral obstructions (n = 5) recruited from 2 companion animal hospitals. Methods: Prospective case-control study. Expression profiles of 24 miRNAs were performed by quantitative PCR (qPCR). Effect of storage temperature (4°C [24 hours], −20°C, and −80°C) was determined for a subset of miRNAs in healthy cats. Results: Urinary miR-4286, miR-30c, miR-204, miR4454, miR-21, miR-16, miR-191, and miR-30a were detected. For the majority of miRNAs tested, storage at 4°C and −20°C resulted in significantly lower miRNA yield compared to storage at −80°C (mean log2fold changes across miRNAs from −0.5 ± 0.4 SD to −1.20 ± 0.4 SD (4°C versus −80°C) and from −0.7 ± 0.2 SD to −1.20 ± 0.3 SD (−20°C versus −80°C)). Cats with PN had significantly upregulated miR-16 with a mean log2fold change of 1.0 ± 0.4 SD, compared with controls (−0.1 ± 0.2, P =.01) and other urological conditions (0.6 ± 0.3, P =.04). Conclusions: Upregulation of miR16 might be PN-specific, pathogen-specific (Escherichia coli), or both.

Background: Specific biomarkers of pyelonephritis (PN) in cats are lacking. MicroRNAs (miRNAs) have diagnostic potential in human nephropathies. Objectives: To investigate the presence/stability of miRNAs in whole urine of cats and the discriminatory potential of selected urinary miRNAs for PN in cats. Animals: Twelve healthy cats, 5 cats with PN, and 13 cats with chronic kidney disease (n = 5), subclinical bacteriuria (n = 3), and ureteral obstructions (n = 5) recruited from 2 companion animal hospitals. Methods: Prospective case-control study. Expression profiles of 24 miRNAs were performed by quantitative PCR (qPCR). Effect of storage temperature (4°C [24 hours], −20°C, and −80°C) was determined for a subset of miRNAs in healthy cats. Results: Urinary miR-4286, miR-30c, miR-204, miR4454, miR-21, miR-16, miR-191, and miR-30a were detected. For the majority of miRNAs tested, storage at 4°C and −20°C resulted in significantly lower miRNA yield compared to storage at −80°C (mean log2fold changes across miRNAs from −0.5 ± 0.4 SD to −1.20 ± 0.4 SD (4°C versus −80°C) and from −0.7 ± 0.2 SD to −1.20 ± 0.3 SD (−20°C versus −80°C)). Cats with PN had significantly upregulated miR-16 with a mean log2fold change of 1.0 ± 0.4 SD, compared with controls (−0.1 ± 0.2, P =.01) and other urological conditions (0.6 ± 0.3, P =.04). Conclusions: Upregulation of miR16 might be PN-specific, pathogen-specific (Escherichia coli), or both.

AGH-44 is described as a selective low-basicity serotonin 7 receptor (5-HT7R) agonist. In this paper, we evaluate if AGH-44 can act as a lead structure to develop a 5-HT7R selective positron emission tomography (PET) tracer. 11C-labeling of AGH-44 succeeded in a two-step, one-pot procedure in good yields. Subsequent PET studies showed that [11C]AGH-44 displays low blood–brain-barrier passage in Long–Evans rats. Moreover, [11C]AGH-44 brain accumulation showed to be independent on permeability glycoprotein (P-gp) efflux inhibition. Results from biodistribution and metabolism studies could neither explain the observed low brain uptake. As such, we believe that this scaffold is not an optimal starting point to develop a 5-HT7R selective PET tracer.

AGH-44 is described as a selective low-basicity serotonin 7 receptor (5-HT7R) agonist. In this paper, we evaluate if AGH-44 can act as a lead structure to develop a 5-HT7R selective positron emission tomography (PET) tracer. 11C-labeling of AGH-44 succeeded in a two-step, one-pot procedure in good yields. Subsequent PET studies showed that [11C]AGH-44 displays low blood–brain-barrier passage in Long–Evans rats. Moreover, [11C]AGH-44 brain accumulation showed to be independent on permeability glycoprotein (P-gp) efflux inhibition. Results from biodistribution and metabolism studies could neither explain the observed low brain uptake. As such, we believe that this scaffold is not an optimal starting point to develop a 5-HT7R selective PET tracer.

Pretargeted nuclear imaging based on the ligation between tetrazines and nano-sized targeting agents functionalized with trans-cyclooctene (TCO) has recently been shown to improve both imaging contrast and dosimetry in nuclear imaging of nanomedicines. Herein, we describe the improved radiosynthesis of a 11 C-labeled tetrazine ([ 11 C]AE-1) and its preliminary evaluation in both mice and pigs. Pretargeted imaging in mice was carried out using both a new TCO-functionalized polyglutamic acid and a previously reported TCO-functionalized bisphosphonate system as targeting agents. Unfortunately, pretargeted imaging was not successful using these targeting agents in pair with [ 11 C]AE-1. However, brain imaging in pig indicated that the tracer crossed the blood-brain-barrier. Hence, we suggest that this tetrazine scaffold could be used as a starting point for the development of pretargeted brain imaging, which has so far been a challenging task.

Pretargeted nuclear imaging based on the ligation between tetrazines and nano-sized targeting agents functionalized with trans-cyclooctene (TCO) has recently been shown to improve both imaging contrast and dosimetry in nuclear imaging of nanomedicines. Herein, we describe the improved radiosynthesis of a 11 C-labeled tetrazine ([ 11 C]AE-1) and its preliminary evaluation in both mice and pigs. Pretargeted imaging in mice was carried out using both a new TCO-functionalized polyglutamic acid and a previously reported TCO-functionalized bisphosphonate system as targeting agents. Unfortunately, pretargeted imaging was not successful using these targeting agents in pair with [ 11 C]AE-1. However, brain imaging in pig indicated that the tracer crossed the blood-brain-barrier. Hence, we suggest that this tetrazine scaffold could be used as a starting point for the development of pretargeted brain imaging, which has so far been a challenging task.

BACKGROUND: The increasing use of the pig as a research model in neuroimaging requires standardized processing tools. For example, extraction of regional dynamic time series from brain PET images requires parcellation procedures that benefit from being automated.COMPARISON WITH EXISTING METHODS: Manual inter-modality spatial normalization to a MRI atlas is operator-dependent, time-consuming, and can be inaccurate with lack of cortical radiotracer binding or skull uptake.NEW METHOD: A parcellated PET template that allows for automatic spatial normalization to PET images of any radiotracer.RESULTS: MRI and [11C]Cimbi-36 PET scans obtained in sixteen pigs made the basis for the atlas. The high resolution MRI scans allowed for creation of an accurately averaged MRI template. By aligning the within-subject PET scans to their MRI counterparts, an averaged PET template was created in the same space. We developed an automatic procedure for spatial normalization of the averaged PET template to new PET images and hereby facilitated transfer of the atlas regional parcellation. Evaluation of the automatic spatial normalization procedure found the median voxel displacement to be 0.22±0.08mm using the MRI template with individual MRI images and 0.92±0.26mm using the PET template with individual [11C]Cimbi-36 PET images. We tested the automatic procedure by assessing eleven PET radiotracers with different kinetics and spatial distributions by using perfusion-weighted images of early PET time frames.CONCLUSION: We here present an automatic procedure for accurate and reproducible spatial normalization and parcellation of pig PET images of any radiotracer with reasonable blood-brain barrier penetration.

BACKGROUND: IInterstitial 21q deletions can cause a wide spectrum of symptoms depending on the size and the location of the deletion. It has previously been suggested that the long arm of chromosome 21 can be divided into three regions based on the clinical severity of the patients and deletion of the region from 32.3 Mb to 37.1 Mb was more crucial than the deletion of other regions.CASE PRESENTATION: In this study we describe a female patient with dysmorphic features, hepatomegaly, thick myocardium and psychomotor delay. Conventional karyotyping was initially interpreted as full monosomy 21, but subsequent chromosome microarray analysis suggested an approximately 18 Mb partial monosomy. Re-evaluation of the karyotype and fluorescence in situ hybridization revealed deletion of the proximal 21q11.2-q22.11 segment and insertion of 21q22.11-qter to 12qter. The deletion of the present case overlaps with two of the proposed regions including part of the proposed crucial region.CONCLUSIONS: This report emphasizes the relevance of investigating suspected full monosomies with high resolution methods and FISH in order to investigate the extent of the deletion and the presence of more complex rearrangements.

BACKGROUND: IInterstitial 21q deletions can cause a wide spectrum of symptoms depending on the size and the location of the deletion. It has previously been suggested that the long arm of chromosome 21 can be divided into three regions based on the clinical severity of the patients and deletion of the region from 32.3 Mb to 37.1 Mb was more crucial than the deletion of other regions.CASE PRESENTATION: In this study we describe a female patient with dysmorphic features, hepatomegaly, thick myocardium and psychomotor delay. Conventional karyotyping was initially interpreted as full monosomy 21, but subsequent chromosome microarray analysis suggested an approximately 18 Mb partial monosomy. Re-evaluation of the karyotype and fluorescence in situ hybridization revealed deletion of the proximal 21q11.2-q22.11 segment and insertion of 21q22.11-qter to 12qter. The deletion of the present case overlaps with two of the proposed regions including part of the proposed crucial region.CONCLUSIONS: This report emphasizes the relevance of investigating suspected full monosomies with high resolution methods and FISH in order to investigate the extent of the deletion and the presence of more complex rearrangements.

BACKGROUND: Congenital cryptorchidism, i.e. failure of the testicular descent to the bottom of the scrotum, is a common birth defect. The evidence from epidemiological, wildlife, and animal studies suggests that exposure to mixtures of endocrine disrupting chemicals during fetal development may play a role in its pathogenesis. We aimed to assess the association between cryptorchidism and prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), and polybrominated diphenyl ethers (PBDEs).METHODS: We conducted a case-control study consisting of 44 cryptorchid cases, and 38 controls operated for inguinal hernia, umbilical hernia, or hydrocele at the Turku University Hospital or Rigshospitalet, Copenhagen in 2002-2006. During the operation a subcutaneous adipose tissue biopsy was taken. Samples were analysed for 37 PCBs, 17 PCDD/Fs and 14 PBDEs by gas chromatography-high-resolution mass spectrometry. Chemical concentrations were adjusted for postnatal variation introduced by differences in duration of breastfeeding, age at the operation, and country of origin with a multiple linear regression. Association between adjusted and unadjusted chemical concentrations and the risk of cryptorchidism were analysed with logistic regression to get an estimate for odds ratio (OR) of cryptorchidism per multiplication of chemical concentrations with ca. 2.71 (Napier's constant).RESULTS: Total-TEq i.e. the WHO-recommended 2,3,7,8-TCDD equivalent quantity of 17 dioxins and 12 dioxin-like PCBs and sum of PCDD/Fs were positively associated with cryptorchidism [OR 3.21 (95% CI 1.29-9.09), OR 3.69 (95% CI 1.45-10.9), respectively], when adjusting for country of origin, the duration the child was breastfed, and age at operation. The association between the sum of PCBs and cryptorchidism was close to significant [OR 1.92 (95% CI 0.98-4.01)], whereas the association between the sum of PBDEs and cryptorchidism was not [OR 0.8

Agents blocking the renin-angiotensin-aldosterone system are frequently used in patients with end-stage renal disease, but whether they exert beneficial cardiovascular effects is unclear. Here the long-term effects of the angiotensin II receptor blocker, irbesartan, were studied in hemodialysis patients in a double-blind randomized placebo-controlled 1-year intervention trial using a predefined systolic blood pressure target of 140 mm Hg (SAFIR study). Each group of 41 patients did not differ in terms of age, blood pressure, comorbidity, antihypertensive treatment, dialysis parameters, and residual renal function. Brachial blood pressure decreased significantly in both groups, but there was no significant difference between placebo and irbesartan. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different. Intermediate cardiovascular end points such as central aortic blood pressure, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal brain natriuretic prohormone, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic blood pressure during the study period significantly correlated with changes in both left ventricular mass and arterial stiffness. Thus, significant effects of irbesartan on intermediate cardiovascular end points beyond blood pressure reduction were absent in hemodialysis patients.

Agents blocking the renin-angiotensin-aldosterone system are frequently used in patients with end-stage renal disease, but whether they exert beneficial cardiovascular effects is unclear. Here the long-term effects of the angiotensin II receptor blocker, irbesartan, were studied in hemodialysis patients in a double-blind randomized placebo-controlled 1-year intervention trial using a predefined systolic blood pressure target of 140 mm Hg (SAFIR study). Each group of 41 patients did not differ in terms of age, blood pressure, comorbidity, antihypertensive treatment, dialysis parameters, and residual renal function. Brachial blood pressure decreased significantly in both groups, but there was no significant difference between placebo and irbesartan. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different. Intermediate cardiovascular end points such as central aortic blood pressure, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal brain natriuretic prohormone, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic blood pressure during the study period significantly correlated with changes in both left ventricular mass and arterial stiffness. Thus, significant effects of irbesartan on intermediate cardiovascular end points beyond blood pressure reduction were absent in hemodialysis patients.

The modeling of corrosion poses particular difficulties. The understanding of corrosion as an electrochemical process has led to simple capacitive-resistive models that take into account the resistance of the electrolytic cell and the capacitive effect of the surface potential at the interface between conductors and the electrolyte. In some models nonlinear conduction effects have been added to account for more complex observed behavior. While these models are sufficient to describe the behavior in systems with cathodic protection, the behavior in the presence of induced AC currents from power lines and from RF sources cannot be accounted for and are insufficient to describe the effects observed in the field. Field observations have shown that a rectifying effect exists that affects the cathodic protection potential and this effect is responsible for corrosion in the presence of AC currents. The rectifying effects of the metal-corrosion interface are totally missing from current models. This work proposes a nonlinear model based on finite element analysis that takes into account the nonlinear behavior of the metal-oxide interface and promises to improve modeling by including the rectification effects at the interface.

The modeling of corrosion poses particular difficulties. The understanding of corrosion as an electrochemical process has led to simple capacitive-resistive models that take into account the resistance of the electrolytic cell and the capacitive effect of the surface potential at the interface between conductors and the electrolyte. In some models nonlinear conduction effects have been added to account for more complex observed behavior. While these models are sufficient to describe the behavior in systems with cathodic protection, the behavior in the presence of induced AC currents from power lines and from RF sources cannot be accounted for and are insufficient to describe the effects observed in the field. Field observations have shown that a rectifying effect exists that affects the cathodic protection potential and this effect is responsible for corrosion in the presence of AC currents. The rectifying effects of the metal-corrosion interface are totally missing from current models. This work proposes a nonlinear model based on finite element analysis that takes into account the nonlinear behavior of the metal-oxide interface and promises to improve modeling by including the rectification effects at the interface.

Udgivelsesdato: 2009-Aug, Accurate prevalence data for acquired cryptorchidism are currently sparse and systematic prospective studies have not yet been reported. Our aim was to determine the prevalence of testicular ascent in childhood. In a prospective longitudinal population-based child cohort from Copenhagen, Denmark (1997-2007), testicular position was examined according to a standardised protocol in a total of 1072 boys, at birth (n = 1051), at 3 months (n = 983), 18 months (n = 888), 36 months (n = 790) and again once between 4 1/2 and 10 years of age (n = 509). Ascensus testis was defined as ascent of the testis into a cryptorchid position after normal scrotal position at birth. A congenital cryptorchid testis with spontaneous postnatal descent followed by recurrence of cryptorchidism was named recurrent cryptorchidism. Ascensus testis occurred in 0.2%, 0.6% and 0.6% of boys at 3, 18 and 36 months of age respectively. When including recurrent cryptorchidism the prevalence was 0.2%, 1.2% and 0.8% respectively. Ascensus testis accounts for 58% of all cases of cryptorchidism (congenital and acquired) at 18 months, 71% at 36 months and thereafter 69%. Ascensus testis accounts for more than half of cryptorchid testes seen in childhood and occurs in both previously scrotal and cryptorchid testes. We therefore recommend that all boys should have testis position checked regularly during childhood, at least up to 3 years of age.

Udgivelsesdato: 2009-Aug, Accurate prevalence data for acquired cryptorchidism are currently sparse and systematic prospective studies have not yet been reported. Our aim was to determine the prevalence of testicular ascent in childhood. In a prospective longitudinal population-based child cohort from Copenhagen, Denmark (1997-2007), testicular position was examined according to a standardised protocol in a total of 1072 boys, at birth (n = 1051), at 3 months (n = 983), 18 months (n = 888), 36 months (n = 790) and again once between 4 1/2 and 10 years of age (n = 509). Ascensus testis was defined as ascent of the testis into a cryptorchid position after normal scrotal position at birth. A congenital cryptorchid testis with spontaneous postnatal descent followed by recurrence of cryptorchidism was named recurrent cryptorchidism. Ascensus testis occurred in 0.2%, 0.6% and 0.6% of boys at 3, 18 and 36 months of age respectively. When including recurrent cryptorchidism the prevalence was 0.2%, 1.2% and 0.8% respectively. Ascensus testis accounts for 58% of all cases of cryptorchidism (congenital and acquired) at 18 months, 71% at 36 months and thereafter 69%. Ascensus testis accounts for more than half of cryptorchid testes seen in childhood and occurs in both previously scrotal and cryptorchid testes. We therefore recommend that all boys should have testis position checked regularly during childhood, at least up to 3 years of age.

Udgivelsesdato: 2008, BACKGROUND: Risk factors for congenital cryptorchidism were investigated in a prospective birth cohort study in Denmark and Finland from 1997 to 2001. METHODOLOGY AND PRINCIPAL FINDINGS: In total, 2,496 boys were examined for cryptorchidism at birth (cryptorchid/healthy: 128/2,368) and three months old (33/2,215). Information on risk factors was obtained antenatally (questionnaire/interview) or at birth from birth records. Use of nicotine substitutes during pregnancy (n = 40) and infertility treatment by intrauterine insemination (n = 49) were associated with an increased risk for cryptorchidism, adjusted odds ratio (95% confidence interval) (OR (95%CI)) 3.04 (95%CI 1.00-9.27) and 3.01 (95%CI 1.27-7.15), respectively. No association was seen for mothers (n = 79) who had infertility treatment in form of intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF) treatment (OR 0.71 95%CI 0.21-2.38). In total, 728 (29%) reported to have smoked during pregnancy, however, no increased risk among maternal smokers was found. Furthermore, we found statistically significant associations between cryptorchidism and low birth weight, prematurity, being small for gestational age, substantial vaginal bleeding, and breech presentation, which are in accordance with other studies. CONCLUSIONS AND SIGNIFICANCE: Our study revealed two novel risk factors for cryptorchidism: intrauterine insemination and the use of nicotine substitutes in pregnancy. This suggests that cryptorchidism may not only be associated to genetic factors, but also to maternal lifestyle and exposure.

Udgivelsesdato: 2008, BACKGROUND: Risk factors for congenital cryptorchidism were investigated in a prospective birth cohort study in Denmark and Finland from 1997 to 2001. METHODOLOGY AND PRINCIPAL FINDINGS: In total, 2,496 boys were examined for cryptorchidism at birth (cryptorchid/healthy: 128/2,368) and three months old (33/2,215). Information on risk factors was obtained antenatally (questionnaire/interview) or at birth from birth records. Use of nicotine substitutes during pregnancy (n = 40) and infertility treatment by intrauterine insemination (n = 49) were associated with an increased risk for cryptorchidism, adjusted odds ratio (95% confidence interval) (OR (95%CI)) 3.04 (95%CI 1.00-9.27) and 3.01 (95%CI 1.27-7.15), respectively. No association was seen for mothers (n = 79) who had infertility treatment in form of intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF) treatment (OR 0.71 95%CI 0.21-2.38). In total, 728 (29%) reported to have smoked during pregnancy, however, no increased risk among maternal smokers was found. Furthermore, we found statistically significant associations between cryptorchidism and low birth weight, prematurity, being small for gestational age, substantial vaginal bleeding, and breech presentation, which are in accordance with other studies. CONCLUSIONS AND SIGNIFICANCE: Our study revealed two novel risk factors for cryptorchidism: intrauterine insemination and the use of nicotine substitutes in pregnancy. This suggests that cryptorchidism may not only be associated to genetic factors, but also to maternal lifestyle and exposure.

Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis.

Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis.

Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis.

Kidney size is an important parameter in the evaluation of children with renal disease. However, reference materials for kidney size in healthy children have been limited beyond the neonatal period. We performed a longitudinal cohort study of 717 healthy children born at term with normal birth weight. Kidney size and shape were determined by ultrasonography and related to gender, age, and body size (weight, length, body surface area, skinfold thickness) at 0, 3, and 18 months of age. Gender-differentiated reference charts were established. Boys had significantly larger kidney volumes than girls ( P<0.001) and larger relative volumes (kidney volume/weight) at 0 and 3 months ( P<0.001), but not at 18 months of age. The best single predictor of gender-differentiated kidney volume was weight. Relative kidney volume changed with increasing age and height in a two-phase pattern: an initial decrease until a height of 65-70 cm was reached followed by a stable level. In conclusion, kidney size was significantly influenced by gender, age, and body composition. Relative kidney volume decreased with increasing age and height in a two-phase pattern. These characteristic changes in kidney volume indicated that infant kidney growth might be influenced by sex steroids and growth hormone in addition to body composition.

Kidney size is an important parameter in the evaluation of children with renal disease. However, reference materials for kidney size in healthy children have been limited beyond the neonatal period. We performed a longitudinal cohort study of 717 healthy children born at term with normal birth weight. Kidney size and shape were determined by ultrasonography and related to gender, age, and body size (weight, length, body surface area, skinfold thickness) at 0, 3, and 18 months of age. Gender-differentiated reference charts were established. Boys had significantly larger kidney volumes than girls ( P<0.001) and larger relative volumes (kidney volume/weight) at 0 and 3 months ( P<0.001), but not at 18 months of age. The best single predictor of gender-differentiated kidney volume was weight. Relative kidney volume changed with increasing age and height in a two-phase pattern: an initial decrease until a height of 65-70 cm was reached followed by a stable level. In conclusion, kidney size was significantly influenced by gender, age, and body composition. Relative kidney volume decreased with increasing age and height in a two-phase pattern. These characteristic changes in kidney volume indicated that infant kidney growth might be influenced by sex steroids and growth hormone in addition to body composition.