Granulocyte colony-stimulating factor has a sex-dependent positive effect in the maternal immune activation-induced autism model.

OBJECTIVE: The medical intervention for autism spectrum disorder (ASD) is restricted to ameliorating comorbid situations. Granulocyte colony-stimulating factor (G-CSF) is a growth factor that enhances the proliferation, differentiation, and survival of hematopoietic progenitor cells. In the present study, we aimed to investigate the effects of G-CSF in a maternal immune activation-induced autism model. METHODS: Sixteen female and six male Wistar adult rats were included in the study. After 21 days, 48 littermates (eight male controls, eight female controls, 16 male lipopolysaccharide [LPS]-exposed rats, and 16 female LPS-exposed rats) were divided into groups. Sixteen male LPS-exposed and 16 female LPS-exposed rats were divided into saline and G-CSF treatment groups. RESULTS: In male rats, the LPS-exposed group was found to have significantly higher levels of TNF-α, IL-2, and IL-17 than the LPS-exposed G-CSF group. Levels of nerve growth factor, brain PSD-95, and brain GAD67 were higher in the LPS-exposed G-CSF group than in the LPS-exposed group in male rats. In female rats, brain NGF levels were similar between groups. There was no difference between groups in terms of brain GAD 67 levels. Brain PSD-95 levels were higher in the control group than in both the LPS-exposed and LPS-exposed G-CSF groups in female rats. Both neuronal CA1 and neuronal CA2 levels were lower, and the GFAP immunostaining index (CA1) and GFAP immunostaining index (CA3) were higher in the LPS-exposed group than in the LPS-exposed G-CSF group in male rats. However, neuronal count CA1 and neuronal count CA3 values were found to be similar between groups in female rats. CONCLUSIONS: The present research is the first to demonstrate the beneficial effects of G-CSF on core symptoms of ASD experimentally depending on male sex. G-CSF can be a good candidate for ameliorating the core symptoms of ASD without serious side effects in males.

Oxidative stress in maternal milk and cord blood in gestational diabetes mellitus: a prospective study

ABSTRACT BACKGROUND: Reduced antioxidant defenses may reflect a poor protective response against oxidative stress and this may be implicated in progression of gestational diabetes mellitus (GDM). Oxidative stress induced by hyperglycemia plays a major role in micro and macrovascular complications, which imply endothelial dysfunction. OBJECTIVE: Our aim in this study was to investigate the association between GDM and oxidative stress markers measured in plasma, with regard to revealing changes to total antioxidant capacity (TAC) and total oxidant status (TOS) among mothers showing impairments in oral glucose tolerance tests (OGTTs). DESIGN AND SETTING: Prospective study at a university hospital in Turkey. METHODS: The study group consisted of 50 mothers with GDM, and 59 healthy mothers served as controls. Umbilical cord blood samples were taken from all mothers during delivery and breast milk samples on the fifth day after delivery. TAC, TOS, thiol and disulfide levels were measured. RESULTS: No statistically significant relationship between the blood and milk samples could be found. An analysis on correlations between TAC, TOS and certain parameters revealed that there were negative correlations between TOS and total thiol (r = -0.386; P < 0.001) and between TOS and disulfide (r = -0.388; P < 0.001) in milk in the control group. However, these findings were not observed in the study group. CONCLUSION: Our findings suggested that a compensatory mechanism of oxidative stress was expected to be present in gestational diabetes mellitus and that this might be ameliorated through good glycemic regulation and antioxidant supplementation.

Oxidative stress in maternal milk and cord blood in gestational diabetes mellitus: a prospective study.

BACKGROUND: Reduced antioxidant defenses may reflect a poor protective response against oxidative stress and this may be implicated in progression of gestational diabetes mellitus (GDM). Oxidative stress induced by hyperglycemia plays a major role in micro and macrovascular complications, which imply endothelial dysfunction. OBJECTIVE: Our aim in this study was to investigate the association between GDM and oxidative stress markers measured in plasma, with regard to revealing changes to total antioxidant capacity (TAC) and total oxidant status (TOS) among mothers showing impairments in oral glucose tolerance tests (OGTTs). DESIGN AND SETTING: Prospective study at a university hospital in Turkey. METHODS: The study group consisted of 50 mothers with GDM, and 59 healthy mothers served as controls. Umbilical cord blood samples were taken from all mothers during delivery and breast milk samples on the fifth day after delivery. TAC, TOS, thiol and disulfide levels were measured. RESULTS: No statistically significant relationship between the blood and milk samples could be found. An analysis on correlations between TAC, TOS and certain parameters revealed that there were negative correlations between TOS and total thiol (r = -0.386; P < 0.001) and between TOS and disulfide (r = -0.388; P < 0.001) in milk in the control group. However, these findings were not observed in the study group. CONCLUSION: Our findings suggested that a compensatory mechanism of oxidative stress was expected to be present in gestational diabetes mellitus and that this might be ameliorated through good glycemic regulation and antioxidant supplementation.

Evaluation of the Relationship Between Attention Deficit Hyperactivity Disorder Symptoms and Chronotype.

INTRODUCTION: The aim of the study is to investigate the relationship between circadian characteristics and behavioral problems in children with Attention Deficit Hyperactivity Disorder (ADHD) (n=53), and to compare this group with healthy controls (n=38). METHOD: Fifty-three medication-free children with ADHD, aged 6-12 years, and 38 healthy children, age and sex matched, participated. Parents completed the Conners' Parent Rating Scale-Revised, the Children's Chronotype Questionnaire (CCTQ), and the Children's Sleep Habits Questionnaire (CSHQ) to assess sleep variables. RESULTS: ADHD children had more sleep-onset problems and parasomnias (in CSHQ) compared to healthy controls. However, circadian preferences did not differ between the groups in CCTQ scores. Another important finding was a mild correlation between parasomnia, bedtime on schooldays, and ADHD symptoms. CONCLUSION: Our study showed that children with ADHD showed more resistance to going to bed than did controls on school days. However, in contrast to our hypothesis, morningness/eveningness preference did not differ from controls in ADHD children.

Do Low Serum UCH-L1 and TDP-43 Levels Indicate Disturbed Ubiquitin-Proteosome System in Autism Spectrum Disorder?

INTRODUCTION: The mechanism of ubiquitination-related abnormalities causing neural development problems is still unclear. We examined the association between autism and serum transactive response DNA-binding protein-43 (TDP-43) and ubiquitin c-terminal hydrolase-L1 (UCH-L1) levels, both of which are members of the ubiquitin-proteosome system. METHODS: We measured serum levels of TDP-43 and UCH-L1 in 24 children with autism and 24 healthy children. Childhood Autism Rating Scale (CARS) was used to assess symptom severity at admission. RESULTS: The mean serum TDP-43 and UCH-L1 levels in children with autism spectrum disorder (ASD) were found to decrease compared to healthy controls (p<0.001, 506.21±780.97 ng/L and 1245.80±996.76 ng/L, respectively; 3.08±5.44 ng/mL and 8.64±6.67 ng/mL, respectively). A positive correlation between serum TDP-43 levels and UCH-L1 levels was found in the ASD group (r=0.947, n=24, p<0.001). The CARS score of children with ASD was 48.91 points (standard deviation [SD]: 5.82). CONCLUSION: Low serum levels of UCH-L1 and TDP-43 may reflect disturbed ubiquitination in autism.

Is children's Body Mass Index associated with their parents' personality? A prospective controlled trial.

BACKGROUND: The aim of this study was to elucidate the effect of the personal characteristics and psychological status of parents on their children's Body Mass Index (BMI) by using validated questionnaires. METHODS: Obese and healthy control group was assessed with The Parental Attitude Research Instrument (PARI) for the evaluation of parental attitudes towards their children. Additionally, Depression Anxiety and Stress Scale (DASS) were used to assess the relationships between parental depression, anxiety, stress and childhood obesity. RESULTS: A total of 105 children and their parents were divided into two groups. The study group consisted of 58 children with a BMI of higher than 85th percentile whereas 47 children with normal BMI (<85th percentile) were included as the control group. In both groups, the BMI of mothers which is between 25-and 30 kg/m2 and >30 kg/m2 had significant impact on the risk of children's obesity status 1.12-fold and 3.68-fold respectively. The PARI results provided that the children who had disciplined, over-protective parents and those in the parental incompatibility group had higher risk of being obese. Analysis of the DASS Test results showed that children having depressed parents had significantly higher risk of obesity than children whose parents were not depressed (P<0.05). CONCLUSIONS: Our results provided that, the parent's status such as obesity, depression and strict personal behaviors have negative impact on their children's weight which is resulting with obesity.

Surgery vs medical treatment in the management of PFAPA syndrome: a comparative trial.

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is a common disorder in children but there is little or no consensus on its optimal diagnosis and management. OBJECTIVES: To compare the outcome of different management approaches - medical therapy or tonsillectomy. METHODS: The medical records of children diagnosed with PFAPA between 2008 and 2013 were retrospectively reviewed according to the modified Thomas test criteria. Patients were divided into two groups: group 1 for medical treatment - corticosteroids, a single intramuscular injection of methylprednisolone, and group 2 for surgery - tonsillectomy alone or tonsillectomy plus adenoidectomy .The course of the disease including the number and duration of episodes and the presence of remission, was documented. RESULTS: 105 patients (30 in group 1, 75 in group 2) met the study's inclusion criteria. Groups 1 and 2 were followed up for a mean (SD) of 23.6 (11.0) and 24 (10.3) months, respectively. At the end of the follow-up period, the number of episodes was 5.8 (6.3) vs 1.8 (1.9) (P<0.01) and their duration was 2.2 (1.3) vs 1.1 (0.8) days (P=0.03), both of which were significantly lower in group 2.The need for hospitalization during this period was significantly lower for group 2 at 1.1 (2.0) vs 0.1 (0.3) (P<0.01) and the remission rate in group 2 was significantly higher than in group 1 (98.6% vs 56.6%, P<0.01). CONCLUSION: This study demonstrated that surgery is superior to medical treatment for PFAPA in terms of increased remission rates and a decrease in the number and duration of episodes.

The relationship between adiponectin levels and epicardial adipose tissue thickness in non-obese children with asthma.

BACKGROUND: There is an association between adiponectin (APN) and asthma. However, the mechanisms underlying this association is unclear. APN is a predominantly anti-inflammatory protein with possible signalling activity in the lung that can be secreted by Epicardial Adipose Tissue (EAT). Our hypothesis is that serum APN levels may be directly and simply related to the amount of EAT accumulation, particularly when it is expressed as thickness in children with asthma. OBJECTIVE: The aim of this study was to investigate whether serum adiponectin (APN) and epicardial adipose tissue thickness (EATT) have an effect in non-obese children with asthma and in healthy non-asthmatic children, and analyze their relationships with clinical outcomes. METHODS: 68 children diagnosed with asthma (20 girls/48 boys) who had applied at the pediatric allergy and clinical immunology clinic of the hospital were included in this cross-sectional, observational study. The age-matched control group included 39 healthy children (18 girls/21 boys). EATT was measured by transthoracic echocardiography. The serum APN levels were also checked. Statistical analysis was performed by using independent sample t-test and Spearman correlation analyses. RESULTS: The mean age of the asthma group was 10.2 ± 2.7 years, and the average EATT was found to be 5.1 ± 0.1 mm. The mean age of the control group was 10.5 ± 2.8 years, and the average EATT was found to be 5.1 ± 0.7 mm. The EATT of the asthma group was found to be significantly higher (p < 0.001) in study group. In the asthma group the APN was 10.0 ± 5.3 mg/L, and in the control group the APN was 15.8 ± 10.5 mg/L (p < 0.001). We found that APN was significantly negatively correlated with EATT (r = -0.266, p = 0.006) in asthma and control groups. CONCLUSION: EATT is associated with non-obese asthmatic children. High EATT may be related with high release of pro-inflammatory cytokine and low release of APN. Low levels of APN may be related to low anti-inflammatory effects. Therefore, high EATT and low levels of APN may indicate pro-inflammantory profiles in non-obese asthmatic children.

Evaluation of the effects of serum iron levels on lacrimal gland secretion.

In our study we aimed to demonstrate the relationship between the serum iron levels, and tears quality and quantity in term newborns. This study was conducted at a single institution between March 2013 and May 2013. A total of 46 newborns were prospectively enrolled. Serum iron levels were measured via the umbilical cord blood. Infants were divided into two groups according to their serum iron levels. Group A, serum iron level ≤70 µg/dL (n = 27) and Group B, serum iron level > 70 µg/dL (n = 19). The evaluation of the osmolarity was tested by using the TearLab Osmolarity System (TearLab Co, San Diego, CA, USA). The assessment of quantity was performed by using Schirmer I test. Osmolarity testing and Schirmer I test (with/without anesthesia) were performed bilaterally on the 1(st) day of life by an ophthalmologist. The outcomes of Schirmer I and tear osmolarity showed no statistically significant difference between right and left eyes of any infant in the groups. Moreover, there was no statistical difference between sexes in these two groups. Osmolarity was found to have a moderate negative correlation coefficient with serum iron level (r = -0.4, p < 0.01). Furthermore, there was a high positive correlation between Schirmer I with anesthesia and serum iron levels (r = 0.7, p < 0.01). We observed that the quality and quantity of the tears was lower in term newborns with lower serum iron levels than healthy newborns. These results indicate that low serum iron level could affect lacrimal gland functions.

Is retrograde flexible nephrolithotripsy feasible for calyceal diverticular stone?

The aim of this study is to manage the calyceal diverticular (CD) stone, several treatment options were applied but it is still a challenging condition of endourology. In this retrospective study, we aim to report the results of our patients with CD stones treated with retrograde flexible nephrolithotripsy (RFNL). A total of 47 patients (55 procedures) who underwent RFNL by a single surgeon for CD stones from January 2004 to March 2013 were evaluated retrospectively. The demographic properties and initial complaints of those patients have been recorded along with their comorbidities and previous history of stone management. Moreover, the size and number of the stones, the duration of the surgery, fluoroscopy time, stone-free rate (SFR) and postoperative complications of the patients have been evaluated. The mean age was 41.8 years (range 16-71). Of the study population, 31 (65.9%) were male. Mean stone size was 21.1 (7-52) mm whereas in 3 (6.4%) of the cases the stones could not be reached. Mean duration of the surgery was 92.8 (57-163) min whereas mean fluoroscopy time was 35.9 (14-103) s. After 3 months of follow-up period, the SFR was 85.1%. No major complications occurred. RFNL with holmium laser and nitinol basket catheter application is a feasible and successful procedure in the management of CD stones. With its high success rates, low incidence of complications and minimal morbidity when compared with other treatment options, RFNL has the potential of becoming the preferred treatment option in the minimally invasive management of patients with CD stones.

Frequency of hematological findings associated with severe plasma vitamin B12 deficiency in infants and adolescents.

BACKGROUND: The aim of this study was to determine the hematological status of severe vitamin B12 deficiency in infants and adolescents. METHODS: This study involved 95 infants and 117 adolescents with severe plasma vitamin B12 deficiency (< 120 pg/ mL) and normal plasma folate and ferritin. Infants were aged between one and 24 months. Adolescents were aged between 11 and 17 years. RESULTS: Macrocytic anemia was associated with nine (9.5%) out of 95 infants with severe vitamin B12 deficiency. Neutropenia was found in 16 (16.8%) out of 95 infants with severe vitamin B12 deficiency. Thrombocytopenia was not found in 95 infants with severe vitamin B12 deficiency. Macrocytic anemia was found in two (1.7%) out of 117 adolescents with a severe vitamin B12 deficiency. Neutropenia was associated in one (0.8%) out of 117 adolescents with severe vitamin B12 deficiency. Thrombocytopenia was not found in 117 adolescents with severe vitamin B12 deficiency. CONCLUSIONS: Low clinical or hematological findings for B12 deficiency in infants and adolescents living in regions at risk, such as those with low consumption of meat and other animal products warrant the measurement of vitamin B12 level.

Responsiveness to parenteral iron therapy in children with oral iron-refractory iron-deficiency anemia.

UNLABELLED: Intravenous (IV) ferric iron (Fe)-carbohydrate complexes are used for treating Fe deficiency in children with iron-refractory iron-deficiency anemia (IRIDA). An optimal treatment has yet to be determined. There are relatively little publications on the responsiveness to IV iron therapy in children with IRIDA. PATIENTS AND METHOD: This study analyzed responses to IV iron sucrose therapy given to 11 children, ranging in age from 2 to 13 years (mean 4.8 years), with iron-deficiency anemia who were unresponsive to oral iron therapy. RESULTS: The hemoglobin and ferritin values (mean) of the 11 children with IRIDA were 7.7 g/dL and 4.8 ng/mL at diagnosis. Both hemoglobin and ferritin levels increased to 9.5 g/dL, and 24 ng/mL, respectively, at 6 weeks after the first therapy. Although the level of hemoglobin was steady at 6 months after the first, and 6 weeks after the second therapy, the ferritin levels continued to increase up to 30 ng/mL and 47 ng/mL at 6 months after the first and 6 weeks after the second therapy, respectively. CONCLUSION: We recommend that IRIDA should be considered in patients presenting with iron-deficiency anemia of unknown cause that is unresponsive to oral iron therapy. Our results suggest that IV iron therapy should be administered only once in cases of IRIDA. Continued administration of IV iron would be of no benefit to increase hemoglobin levels. On the contrary, ferritin levels may continue to increase resulting in untoward effects of hyperferritinemia.

Treatment of renal stones with flexible ureteroscopy in preschool age children.

The aim of the study is to evaluate the efficacy and safety of retrograde intrarenal surgery (RIRS) to treat renal stones in preschool age (<7 years) children. From September 2005 to May 2013, a total of 65 children (31 boys and 34 girls) with 72 renal stones were treated using RIRS. Patients were considered stone-free when the absence of residual fragments was observed on imaging studies. In the presence of residual calculi >4 mm, a second-stage RIRS was performed. The pre-operative, operative and post-operative data of the patients were retrospectively analyzed. A total of 65 patients with a mean age of 4.31 ± 1.99 years (6 months-7 years) were included in the present study. The mean stone size was 14.66 ± 6.12 mm (7-30 mm). The mean operative time was 46.47 ± 18.27 min. In 5 (7.69%) patients, the initial procedure failed to reach the renal collecting system and ended with the insertion of a pigtail stent. The stone-free rates were 83.07 and 92.3% after the first and second procedures, respectively. Complications were observed in 18 (27.7%) patients and classified according to the Clavien system. Post-operative hematuria (Clavien I) occurred in 6 (9.2%) patients, post-operative urinary tract infection with fever (Clavien II) was observed in 10 (15.4%) patients, and ureteral wall injury (Clavien III) was noted in 2 (3%) patients. RIRS is an effective and safe procedure that can be used to manage renal stones in preschool age children.

LRIG2 mutations cause urofacial syndrome.

Urofacial syndrome (UFS) (or Ochoa syndrome) is an autosomal-recessive disease characterized by congenital urinary bladder dysfunction, associated with a significant risk of kidney failure, and an abnormal facial expression upon smiling, laughing, and crying. We report that a subset of UFS-affected individuals have biallelic mutations in LRIG2, encoding leucine-rich repeats and immunoglobulin-like domains 2, a protein implicated in neural cell signaling and tumorigenesis. Importantly, we have demonstrated that rare variants in LRIG2 might be relevant to nonsyndromic bladder disease. We have previously shown that UFS is also caused by mutations in HPSE2, encoding heparanase-2. LRIG2 and heparanase-2 were immunodetected in nerve fascicles growing between muscle bundles within the human fetal bladder, directly implicating both molecules in neural development in the lower urinary tract.

Relation between 3435C>T multidrug resistance 1 gene polymorphism with high dose methylprednisolone treatment of childhood acute idiopathic thrombocytopenic purpura.

UNLABELLED: The current study was conducted to assess 3435C>T multidrug resistance 1 gene polymorphism and the efficacy of high dose methylprednisolone (HDMP) in childhood acute idiopathic thrombocytopenic purpura patients. METHODS: A total of 31 childhood acute Idiopathic thrombocytopenic purpura patients (17 females, 14 males) between the ages of 2 and 16 years of age were included in the study. High-dose methylprednisolone was given at a dose of 30mg/kg/day for 3 days and 20mg/kg/day for 4 days, consecutively and intravenously. Polymerase chain reaction-restriction fragment length polymorphism was used for the detection of C3435T single nucleotide polymorphism. Fragments obtained were 238bp to T/T genotype, 172bp and 60bp fragments to the C/C genotype, and 238bp, 172bp and 60bp to the C/T genotype. RESULTS: The distribution of CC, CT, and TT genotypes were 19.0%, 61.3%, and 19.4%, respectively. Both allele frequencies of C and T were the same - 50%. There was no significant difference in genotype and allele distribution between the patients with ITP and the control group (χ(2)=0.84 p=0.65, χ(2)=0.2 p=0.63, respectively). There were no significant differences in age, gender, and pre- and post-treatment platelet counts between CC, CT, and TT genotypes of the MDR gene. Response to treatment shows no significant difference between genotype and allele groups. CONCLUSION: In our study, there was no difference in the HDMP treatment response between MDR1 gene genotypes. However, it should be noted that this study includes a small group of patients. Our data should therefore be considered preliminary, awaiting further confirmatory studies on an expanded patient base.