A Phase I clinical trial of dose-escalated metabolic therapy combined with concomitant radiation therapy in high-grade glioma.

BACKGROUND: Animal brain-tumor models have demonstrated a synergistic interaction between radiation therapy and a ketogenic diet (KD). Metformin has in-vitro anti-cancer activity, through AMPK activation and mTOR inhibition. We hypothesized that the metabolic stress induced by a KD combined with metformin would enhance radiation's efficacy. We sought to assess the tolerability and feasibility of this approach. METHODS: A single-institution phase I clinical trial. Radiotherapy was either 60 or 35 Gy over 6 or 2 weeks, for newly diagnosed and recurrent gliomas, respectively. The dietary intervention consisted of a Modified Atkins Diet (ModAD) supplemented with medium chain triglycerides (MCT). There were three cohorts: Dietary intervention alone, and dietary intervention combined with low-dose or high-dose metformin; all patients received radiotherapy. Factors associated with blood ketone levels were investigated using a mixed-model analysis. RESULTS: A total of 13 patients were accrued, median age 61 years, of whom six had newly diagnosed and seven with recurrent disease. All completed radiation therapy; five patients stopped the metabolic intervention early. Metformin 850 mg three-times daily was poorly tolerated. There were no serious adverse events. Ketone levels were associated with dietary factors (ketogenic ratio, p < 0.001), use of metformin (p = 0. 02) and low insulin levels (p = 0.002). Median progression free survival was ten and four months for newly diagnosed and recurrent disease, respectively. CONCLUSIONS: The intervention was well tolerated. Higher serum ketone levels were associated with both dietary intake and metformin use. The recommended phase II dose is eight weeks of a ModAD combined with 850 mg metformin twice daily.

Protective effect of soluble Klotho in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass support-A pilot study.

OBJECTIVE: The Klotho protein family plays important roles in several metabolic pathways. Soluble Klotho has been recently put forward as an antiaging protein, demonstrating renal and cardiovascular protective traits. Cardiopulmonary bypass (CPB) support during cardiac surgery has been implicated in several adverse outcomes in pediatric and adult patients. Our goal was to assess whether serum Klotho levels can be used to predict outcomes in children undergoing cardiac surgery with CPB due to congenital heart defects (CHDs). METHODS: This prospective study was conducted on pediatric patients admitted to two Pediatric Cardiac Intensive Care Units, between 2012 and 2018. All patients were born with CHD and underwent corrective surgery with CPB. Sequential blood samples were analyzed by enzyme-linked immunosorbent assay for soluble Klotho levels at baseline, 2, 6, and 24 h after surgery. The association between Klotho levels and several demographic, intraoperative, and postoperative clinical and laboratory parameters was studied. RESULTS: Twenty-nine children undergoing cardiac surgery with CPB support were included. Serum Klotho levels were shown to significantly decrease 2 h after surgery and increase to baseline levels after 6 h (p < .001 and p < .05, respectively). Patients with low Klotho levels 2 h after surgery were at a 32-fold higher risk for developing postoperative complications (p = .015, odds ratio < 0.03). Moreover, Klotho levels at each of the four time points were lower in patients who developed postoperative complications. CONCLUSIONS: Cardiac surgery with CPB results in a significant decrease of serum Klotho levels 2 h after surgery in pediatric patients with CHDs, which can be used to predict development of postoperative complications in this patient population.

The metabolic syndrome and its components in pediatric survivors of allogeneic hematopoietic stem cell transplantation.

Metabolic syndrome (MetS) is a known complication after hematopoietic stem cell transplantations (HSCT) that contributes to long-term morbidity. We assessed the prevalence of components of the MetS in pediatric survivors of allogeneic HSCT and identified associated risk factors. Thirty-eight patients, median age at HSCT, 8.5 years, were evaluated at a median of 3.9 years post-HSCT. Overweight or obesity was seen in 23.7% of the patients, 15.8% had hypertension, 15.8% had hypertriglyceridemia, and 13% had low high-density lipoprotein cholesterol levels according to age and gender. Four (10.5%) met the criteria of MetS; all were transplanted for malignant disease. Twelve patients (31.6%) had at least one component of the MetS. The 5-year probability of developing components of the MetS revealed that patients with BMI-Z score ≥0 at HSCT were significantly at higher risk than those with lower BMI-Z. Patients who developed components of the MetS had higher levels of insulin, homeostasis model assessment, uric acid, leptin, and lower adiponectin levels. Multivariable regression analysis revealed that BMI-Z-score >1.036 at time of evaluation was associated with 4.3-fold increased risk (P=.050) and adiponectin levels ≤6 µg/mL were associated with 6.7-fold increased risk of develop components of the MetS (P=.007). Overweight and obesity and adiponectin levels may be useful as markers in HSCT survivors.

Epilepsy and behavioral changes, type 1 diabetes mellitus and a high titer of glutamic acid decarboxylase antibodies.

Autoantibodies to the 65 kDa isoform of glutamate acid decarboxylase (GAD65Ab) are associated with a range of clinical disorders, including type 1 diabetes (T1D) and stiff-person syndrome (SPS). In this article we describe a young girl who was diagnosed with T1D at the end of her first year of life and developed drug-resistant epilepsy 18 months later, followed by behavioral disturbances. She was admitted to our center at the age of 5 yr, at which time high GAD65Ab titers were detected in the patient's serum and cerebrospinal fluid (CSF). The titer remained elevated during 19 months of follow-up. Furthermore, GAD65Ab in both serum and CSF showed epitope binding characteristics similar to those observed for GAD65Ab in SPS patients, and GAD65Ab in the serum reduced GAD65 enzyme activity. Our results suggest an association between high GAD65Ab titers and epilepsy in children with T1D. Careful titration and characterization of GAD65Ab regarding inhibition of enzyme activity and epitope specificity may be helpful in identifying T1D patients at risk for neurological complications.

Persistent Müllerian Duct Syndrome Caused by a Novel Mutation of an Anti-MüIlerian Hormone Receptor Gene: Case Presentation and Literature Review.

Persistent Müllerian duct syndrome (PMDS) is a rare genetic disorder of male internal sexual development defined as lack of regression of Müllerian derivatives in the 46XY male with normally virilized external genitalia and unilateral or bilateral cryptorchidism. Approximately 85% of all cases are caused by mutations in genes encoding anti-Müllerian hormone (AMH) or its receptor (AMHR2) with autosomal recessive transmission. This condition is frequently diagnosed incidentally, during surgical repair of inguinal hernia or cryptorchidism. There is no consensus on surgical approach: malignancy risk in the Müllerian duct remnant or undescended testis encourages early removal of the former and bilateral orchiopexy; however, removal of Müllerian structures can impair testicular and vas deferens blood supply, potentially causing infertility. Herein, we report on a male infant with PMDS caused by a novel homozygous missense mutation in AMHR2 (c.928C>T; p.Q310X), review the literature, and discuss the diverse clinical and surgical approaches to this condition.

Omentin, an adipokine with insulin-sensitizing properties, is negatively associated with insulin resistance in normal gestation.

OBJECTIVE: Omentin, a newly identified adipokine, enhances insulin mediated glucose uptake in human adipocytes, thus, inducing systemic insulin-sensitizing effect. The aims of this study were to determine whether circulating maternal omentin levels are associated with insulin resistance indices and to assess which compartment, maternal, fetal, or placental, is the source of omentin in maternal circulation. METHODS: Fasting serum glucose, insulin, and omentin were determined in 25 healthy pregnant women at the third trimester, before and 3 days after elective cesarean section. Cord blood omentin was measured in the 25 term neonates. Homeostasis model assessment (HOMA) was used to evaluate insulin sensitivity before and after delivery. RESULTS: Antepartum maternal omentin levels were negatively correlated with insulin levels (r=-0.41, P=0.04) and positively correlated with insulin sensitivity (HOMA%S; r=0.4, P=0.04). Postpartum omentin levels were negatively correlated with maternal body mass index (r=-0.44, P=0.02). Median maternal omentin levels was comparable before and after delivery (57.2, inter-quartile range: 38.2-76.2 ng/mL vs. 53.4, 39.8-69.4 ng/mL, respectively, P=0.25) and highly correlated (r=0.83, P<0.001). Antepartum maternal and neonatal omentin levels did not differ significantly (fetal: 62.2, 44.3-74.2 ng/mL, P=0.77) and did not correlate (P=0.6). CONCLUSIONS: Circulating maternal omentin levels are correlated with insulin resistance indices, suggesting that this adipokine may play a role in metabolic adaptations of normal gestation. The strong correlation between anteparum and postpartum maternal omentin levels, as well as the lack of association between maternal and neonatal omentin levels, suggest that placental or fetal compartments are unlikely as the main source of circulating maternal omentin.

Chemerin concentrations in maternal and fetal compartments: implications for metabolic adaptations to normal human pregnancy.

OBJECTIVES: Chemerin, a novel adipocytokine, has been implicated in major metabolic and inflammatory processes. Study aims were to determine whether circulating maternal chemerin concentration (1) differs between pregnant and non-pregnant women, (2) changes as a function of gestational age, and (3) correlates with maternal insulin resistance. In addition, we investigated which compartment, maternal, fetal or placental, is the source of chemerin in maternal circulation. METHODS: The study included three groups: Non-pregnant (n=18), pregnant women in the first trimester (n=19) and pregnant women in the third trimester (n=33). Chemerin was measured in cord blood and in maternal serum samples taken before and after delivery. Chemerin mRNA expression was evaluated in fetal and human adult tissues. RESULTS: Chemerin serum concentration was significantly higher in pregnant women in the third trimester than in non-pregnant and pregnant women in the first trimester. Chemerin concentration positively correlated with body mass index (BMI) and insulin resistance. Antenatal chemerin concentration was significantly lower than that during the postpartum period. Neonatal chemerin did not correlate with maternal one. Chemerin mRNA expression was abundant in fetal and adult liver and omental fat, but relatively low in placenta. CONCLUSIONS: Chemerin is increased during normal gestation and is associated with maternal BMI and insulin resistance. Maternal tissues, possibly liver and adipose tissue, contribute to the increased maternal chemerin concentration.

Anti-Müllerian hormone (AMH) downregulation in late antral stages is impaired in PCOS patients. A study in normo-ovulatory and PCOS patients undergoing in vitro maturation (IVM) treatments.

PURPOSE: To prospectively study the AMH expression and secretion pattern in mural granulosa cells (GCs) and follicular fluid (FF) from small follicles and medium follicles that were collected from normo-ovulatory (NO) and polycystic ovary syndrome (PCOS) patients undergoing in vitro maturation (IVM) treatments. METHODS: FF AMH levels and mRNA expression of mural GCs were measured in small (≤ 10 mm) and medium size follicles (11-15 mm) obtained from IVM treatments and large size follicles (≥ 16 mm) obtained from in vitro fertilization treatments. RESULTS: First, we show that AMH expression and protein level in the FF of NO patients were significantly higher in the small size follicles than in the medium and large size follicles (p < 0.003). We could not demonstrate these differences in PCOS patients. Second, we found significantly higher levels of AMH protein and mRNA in the large and medium (but not small) size follicles of PCOS patients compared to follicles from NO patients (p < 0.02). Finally, we observed a positive correlation between FF AMH of small and medium size follicles from NO patients and serum AMH (p < 0.03 and p < 0.0002, respectively). CONCLUSIONS: Our data demonstrate a pathological dysregulation of AMH expression and secretion in follicles from PCOS patients and emphasize the association between the physiological downregulation of AMH and follicular antral health.

Chemerin is present in human cord blood and is positively correlated with birthweight.

OBJECTIVE: Chemerin, a novel adipokine, has been implicated in adipogenesis, inflammation, and metabolism. The aims of this study were to determine the presence of chemerin in cord blood and its association with birthweight. STUDY DESIGN: This cross-sectional study included the following: (1) twins with (n = 24) or without (n = 28) birthweight discordancy; and (2) singletons subclassified into small-for-gestational-age (SGA; n = 18); appropriate for gestational age (AGA; n = 33); and large-for-gestational-age (LGA; n = 8). Cord blood chemerin was determined. Parametric and nonparametric statistics were used for analysis. RESULTS: The results of the study included the following: (1) within the discordant twins group, the median chemerin concentration was significantly lower in the SGA group than in their cotwins; (2) within singletons, the median chemerin concentration was significantly higher in the LGA than the AGA newborns; and (3) the regression model revealed that chemerin was independently associated with birthweight. CONCLUSION: Cord blood chemerin is present in cord blood and its concentrations are positively correlated with birthweight. These novel findings support a role of adipokines in fetal growth.

Vitamin D status in pediatric patients with a history of malignancy.

BACKGROUND: Multiple studies associate low vitamin D levels with cancer morbidity and mortality. However, few studies have measured vitamin D in pediatric patients with malignancy. Our aim was to assess vitamin D status in a large cohort of pediatric patients with cancer and to define risk factors for deficiency. METHODS: Circulating 25-hydroxyvitamin D (25OHD) levels were measured in 211 patients. Calcium intake and sun exposure habits were assessed in 142 patients (age 12.1 ± 5.8 y; number of male patients, 69; mean time from diagnosis, 4.4 ± 3.8 y). RESULTS: Daily calcium intake was 66.2 ± 39.3% of the recommended daily allowance. Mean 25OHD levels were 20.6 ± 7.9 ng/ml. Vitamin D deficiency (<15 ng/ml) was found in 24.6% of the patients and insufficiency (15-20 ng/ml) in 23.2%. Younger age and amount of sun exposure were associated with higher serum 25OHD. No association was found with calcium intake, disease type, gender, BMI SD score, years since diagnosis, or stem cell transplantation. The 25OHD levels during winter were significantly lower than the summer levels. CONCLUSION: The prevalence of vitamin D deficiency and insufficiency in pediatric patients with a history of malignancy was high, whereas calcium intake was low. These findings are concerning, given the risk for osteoporosis in this population and the possible role of vitamin D in the context of malignancy.

Evaluation of leptin levels among fibromyalgia patients before and after three months of treatment, in comparison with healthy controls.

BACKGROUND: Leptin, an adipocyte-produced cytokine, interacts with various hormones, including those of the hypothalamic-pituitary-adrenal axis. Fibromyalgia is a syndrome characterized by widespread pain accompanied by tenderness. The pathogenesis involves a disturbance in pain processing and transmission by the central nervous system, leading to a general increase in pain perception. OBJECTIVES: To analyze potential changes in leptin levels among female fibromyalgia patients compared with healthy controls, and to evaluate the changes in leptin levels during treatment. METHODS: Sixteen female fibromyalgia patients were recruited. Patients underwent clinical evaluation, physical examination, including manual dolorimetry, and were evaluated regarding quality of life, pain, fatigue, anxiety and depression. Plasma leptin levels were determined by ELISA. Patients were offered standard treatment for fibromyalgia. Clinical evaluation and leptin determination were repeated after three months. RESULTS: No significant difference was observed between leptin levels among fibromyalgia patients and controls; no significant correlation was observed between leptin levels and clinical parameters reflecting fibromyalgia severity; and no significant change was observed in leptin levels over three months of treatment. These results did not change after adjustment of leptin levels for body mass index values. CONCLUSIONS: The results of the present study do not support the existence of a significant relationship between leptin and fibromyalgia pathogenesis. Increasing the sample size or examining the interaction between leptin and additional hormones/mediators of metabolism and body weight control may yet uncover significant information in this field.

Expression and regulation of sFRP family members in human granulosa cells.

Follicular development and ovulation are major processes in the reproductive system. Understanding their complexity is important to female fertility treatments and the control of reproductive processes. Wnt signaling pathway components were shown to be involved in reproduction in animal models. The secreted frizzled-related protein-4 (sFRP4), a potential modulator of Wnt4 signaling pathway, was shown to be induced by LH in rodents and expressed in the corpus lutea, but the pattern of its expression in human ovaries remains unknown. We evaluated the expression pattern of sFRP4 and other sFRP family members in human mural and cumulus granulosa cells (GCs), as well as their regulation by LH/hCG. GCs were obtained from follicles aspirated during in vitro maturation and IVF procedures. GCs were also plated and grown in culture. We showed that the human sFRP4 expression decreases as follicles grows to the preovulatory stage and its expression was higher in cumulus GCs than in mural GCs. Interestingly, LH/hCG stimulation of GCs in vivo and in culture resulted in decreased expression of sFRP4. Of the other sFRP family members, sFRP5 expression was found in mural and cumulus GC in vivo and was shown to be induced by LH/hCG in vitro and in vivo. In summary, sFRP4 is expressed in human GCs and its expression declines during late antral follicular growth. sFRP4 expression is also inhibited by LH/hCG, unlike its rodent homolog. In human GC, sFRP5 may substitute the role of sFRP4 in mouse GC.

Insulin sensitivity in late gestation and early postpartum period: the role of circulating maternal adipokines.

OBJECTIVE: Early postpartum period is characterised by a dramatic decrease in insulin resistance and significant metabolic alterations. The aims of this study were to determine the changes in circulating maternal concentrations of total adiponectin, adiponectin multimers, leptin and resistin before and after the delivery and to explore their relationship with insulin sensitivity. METHODS: Twenty-seven normal pregnant women at term were included in this longitudinal study. Blood samples were taken before and 4 days after elective caesarean section. Total adiponectin, adiponectin multimers, leptin, resistin, glucose, insulin and prolactin were measured in maternal serum. Adiponectin multimers were measured before and after the delivery in eight women. RESULTS: (1) The mean maternal serum total adiponectin concentration was significantly higher before than after delivery while the relative distribution of circulating maternal adiponectin multimers did not change after delivery; (2) the median maternal serum concentration of leptin was significantly higher in the antepartum than in the postpartum period; (3) the median maternal serum resistin concentration was comparable before and after delivery; (4) multiple linear regression analysis revealed that antepartum insulin sensitivity was associated with maternal low body mass index, and low glucose concentrations in glucose challenge test, as well as with maternal age and increased leptin concentrations. Postpartum insulin sensitivity was associated with decreased circulating resistin concentrations. CONCLUSIONS: Despite increase in insulin sensitivity, early postpartum period is characterised by a decrease in maternal circulating total adiponectin and by steady concentrations of resistin and adiponectin multimers compared to the late third trimester.

Cord blood adiponectin and infant growth at one year.

OBJECTIVE: The aim of this study was to determine the association between cord blood adiponectin and leptin and early infant growth at one year in small for gestational age (SGA) and appropriate for gestational age (AGA) infants. STUDY DESIGN: In this prospective study adiponectin and leptin concentrations were determined in cord blood of (i) AGA newborns (n = 44) and (ii) SGA newborns (n = 24). At one year of age, height and weight were measured. Linear regression analysis was used to determine which factors were associated with anthropometric measurements at the age of one year. RESULTS: (i) SGA neonates had a significantly lower median cord blood adiponectin and leptin than AGA neonates; (ii) among SGA neonates, cord blood adiponectin concentrations were negatively correlated with body weight at one year, weight gain after one year and with BMI at one year; and (iii) among AGA neonates cord blood adiponectin concentrations were negatively correlated with body weight at one year, weight gain after one year and with BMI at one year. CONCLUSION: The disparity in cord blood adiponectin and leptin concentrations between SGA and AGA neonates suggests a role for adipokines in fetal growth.

Serologic bone markers for predicting development of osteonecrosis of the jaw in patients receiving bisphosphonates.

PURPOSE: Osteonecrosis of the jaw is a well-documented side effect of bisphosphonate (BP) use. Attempts have recently been made to predict the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We prospectively investigated the predictive value of serum levels of C-terminal telopeptide of collagen I (CTX), bone-specific alkaline phosphatase, and parathyroid hormone for the development of BRONJ. PATIENTS AND METHODS: Data on the demographics, comorbidities, and BP treatment were collected from 78 patients scheduled for dentoalveolar surgery. Of the 78 patients, 51 had been treated with oral BPs and 27 had been treated with frequent intravenous infusions of BPs. Blood samples for CTX, bone-specific alkaline phosphatase, and parathyroid hormone measurements were taken preoperatively. Surgery was performed conservatively, and antibiotic medications were prescribed for 7 days. RESULTS: Of the 78 patients, 4 patients taking oral BPs (7.8%) and 14 receiving intravenous BPs (51.8%) developed BRONJ. A CTX level less than 150 pg/mL was significantly associated with BRONJ development, with an increased odds ratio of 5.268 (P = .004). The bone-specific alkaline phosphatase levels were significantly lower in patients taking oral BPs who developed BRONJ. The parathyroid hormone levels were similar in patients who did and did not develop BRONJ. CONCLUSION: The incidence of BRONJ after oral surgery involving bone is greater among patients receiving frequent, intravenous infusions of BPs than among patients taking oral BPs. Although the measurement of serum levels of CTX is not a definitive predictor of the development of BRONJ, it might have an important role in the risk assessment before oral surgery.

Adiponectin levels in adolescent girls with polycystic ovary syndrome (PCOS).

OBJECTIVE: To determine serum adiponectin concentrations in adolescent girls with and without polycystic ovary syndrome (PCOS) and to assess possible correlations of adiponectin levels with insulin and androgen levels. DESIGN: Prospective case-control study. SETTING: Endocrine clinics in the community. PATIENTS: Forty-four adolescent girls were grouped as follows: 14 were overweight [body mass index (BMI) standard deviation score >1.645] with PCOS; 16 were lean (BMI SDS <1.036) with PCOS; and 14 were lean (BMI SDS <1.036) without PCOS. Intervention Blood samples were collected from all girls between 8 and 11 am, after an overnight fast. MAIN OUTCOME MEASURES: Serum levels of adiponectin, leptin, insulin, Müllerian-inhibiting substance, luteinizing hormone, follicle-stimulating hormone, testosterone, 17-alpha-hydroxyprogesterone, androstendione, dehydroepiandrosterone sulphate (DHEAS) and 17beta-oestradiol. RESULTS: Adiponectin concentrations were significantly decreased in obese adolescents with PCOS (10.5 +/- 5.5 mug/ml) compared with that in lean girls with or without PCOS (16.9 +/- 8.64 and 18.0 +/- 7.4 mug/ml respectively). Leptin levels were significantly elevated in obese adolescents with PCOS compared with the levels in normal weight adolescents with PCOS, and compared with that in normal weight controls. Insulin levels were markedly higher in obese adolescents with PCOS compared with that in normal weight adolescents (12.3 +/- 12.2 vs. 4.5 +/- 2.9, P < 0.05), and compared with that in normal weight PCOS adolescents (7.4 +/- 4.9); however, this difference was not statistically significant. Insulin levels did not differ between normal weight adolescents with PCOS and normal controls. Adiponectin concentrations correlated inversely with BMI, leptin and insulin. CONCLUSIONS: Hypoadiponectinaemia is evident only in obese adolescents with PCOS and therefore does not seem to be involved in the pathogenesis of PCOS in this age group.

Early diagnosis of gestational diabetes mellitus using circulating microRNAs.

DESIGN: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and its prevalence is constantly rising worldwide. Diagnosis is commonly in the late second or early third trimester of pregnancy, though the development of GDM starts early; hence, first-trimester diagnosis is feasible. OBJECTIVE: Our objective was to identify microRNAs that best distinguish GDM samples from those of healthy pregnant women and to evaluate the predictive value of microRNAs for GDM detection in the first trimester. METHODS: We investigated the abundance of circulating microRNAs in the plasma of pregnant women in their first trimester. Two populations were included in the study to enable population-specific as well as cross-population inspection of expression profiles. Each microRNA was tested for differential expression in GDM vs control samples, and their efficiency for GDM detection was evaluated using machine-learning models. RESULTS: Two upregulated microRNAs (miR-223 and miR-23a) were identified in GDM vs the control set, and validated on a new cohort of women. Using both microRNAs in a logistic-regression model, we achieved an AUC value of 0.91. We further demonstrated the overall predictive value of microRNAs using several types of multivariable machine-learning models that included the entire set of expressed microRNAs. All models achieved high accuracy when applied on the dataset (mean AUC = 0.77). The significance of the classification results was established via permutation tests. CONCLUSIONS: Our findings suggest that circulating microRNAs are potential biomarkers for GDM in the first trimester. This warrants further examination and lays the foundation for producing a novel early non-invasive diagnostic tool for GDM.

Adipose stress-sensing kinases: linking obesity to malfunction.

Obesity has been proposed to inflict a variety of stresses on adipose tissue, including inflammatory, metabolic, oxidative and endoplasmic reticulum stress. Through the activation of 'stress-sensing pathways', metabolic and endocrine alterations are produced, which probably contribute to the co-morbidities associated with obesity. Here, we review the evidence supporting the development of various obesity-related stresses and the activation of several stress-sensing pathways, specifically in adipocytes and/or adipose tissue, which manifest metabolic and endocrine dysfunction frequently in obesity. As the central role of adipose tissue in regulating whole-body metabolism is elucidated, understanding adipose tissue stress-sensing pathways might provide potential new therapeutic targets to attenuate obesity-related morbidity.

The Impact of Preterm Infants' Continuous Exposure to Breast Milk Odor on Stress Parameters: A Pilot Study.

OBJECTIVE: This pilot study aimed to assess the effect of continuous exposure to the odor of own mothers' breast milk (BM) on the stress parameters of preterm infants. MATERIALS AND METHODS: Fifteen healthy preterm infants were included. Mean heart rate and salivary cortisol were measured over three consecutive time periods, each lasting 2 days: (1) preintervention (odor free); (2) intervention, during which a cotton pad soaked with 1.5 mL of BM was placed near the infant's head with the aim of providing continuous exposure to its odor; (3) postintervention period (odor free). RESULTS: Saliva cortisol levels differed significantly between the three exposure periods (pre-, during, and post-BM odor exposure): 11.38 ± 5.03, 9.51 ± 4.38, and 4.99 ± 3.42 nmol/L, respectively. A repeated univariate analysis of the cortisol measure showed a significant difference (F = 9.34; df = 2.28, p < 0.001). There was no difference in mean heart rate over the three study periods. CONCLUSIONS: Preterm infants exposed to BM odor from their own mothers demonstrate a persistent decrease in saliva cortisol levels, which continues after termination of the intervention. This finding may suggest that exposure to own mothers' BM odor has a soothing effect on preterm infants. Further randomized controlled studies are needed to evaluate this simple, safe, and inexpensive intervention.

Modulation of adiponectin and leptin during refeeding of female anorexia nervosa patients.

CONTEXT: Several studies assessed adiponectin levels in anorexia nervosa (AN) patients, however, data regarding the dynamics of changes in adiponectin levels during refeeding of these patients is limited and contradicting. OBJECTIVE: Our objective was to assess adiponectin levels and the distribution of its different isoforms in AN patients before and after long-term refeeding, and to relate them to alterations in body mass index, leptin, insulin sensitivity, and additional endocrine parameters. DESIGN, SETTING, AND PARTICIPANTS: We conducted a longitudinal controlled study of 38 female adolescent malnourished AN inpatients, with 13 young, lean, healthy women serving as controls. Blood samples were obtained upon admission and thereafter at 1, 3, and 5 months (at target weight). MAIN OUTCOME MEASURES: Changes in body mass index, leptin, adiponectin, insulin sensitivity, and adiponectin multimeric forms were measured. RESULTS: At admission, leptin levels of AN patients were significantly lower, whereas insulin sensitivity (assessed by homeostasis model assessment-insulin resistance), adiponectin levels, and the ratio of high molecular weight (HMW) adiponectin to total adiponectin were significantly higher compared with controls. During weight recovery, leptin levels and homeostasis model assessment-insulin resistance increased significantly, whereas adiponectin and HMW adiponectin/total adiponectin ratio decreased significantly, to levels similar to controls. An initial increase in adiponectin levels was observed after 1 month of refeeding. There was no correlation between adiponectin and either T(4) or cortisol levels. CONCLUSIONS: Our study demonstrates hyperadiponectinemia, increased adiponectin HMW isoform, and increased insulin sensitivity in adolescent AN female patients and reversal of these findings with weight rehabilitation. We hypothesize that increased adiponectin levels may have a protective role in maintaining energy homeostasis during extreme malnourishment.