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Bone marrow transplantation (BMT) recipients are at risk of bone mass impairment and skeletal morbidity. We investigated bone status with quantitative ultrasound (QUS) technique in children and adolescents with hematological diseases before and after BMT.Phalangeal QUS measures for amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were obtained in 144 hematological patients (81M, 63F; 11.6+/-5.2 years); forty two were evaluated before BMT and 102 after allogeneic or autologous BMT. Bone parameters were expressed as Z-scores based on age-sex-matched normal controls.Mean BTT Z-score was reduced in subjects after BMT compared to patients before BMT (M, -0.35+/-1.04 vs. 0.70+/-1.11, P0.001; F, -0.60+/-1.23 vs. 0.23+/-1.17, P0.05). Females and males with hormone deficiencies showed reduced BTT Z-scores when compared with subjects without hormone defects (M, -0.52+/-1.0 vs. 0.05+/-1.17, P0.05; F, -0.50+/-1.27 vs. -0.19+/-1.26; P=0.06). AD-SoS and BTT Z-scores were reduced in 15 subjects with fractures and/or avascular osteonecrosis compared to patients without bone events (-1.52+/-1.7 vs. -0.41+/-1.32 and -0.85+/-1.19 vs. -0.10+/-1.18; both Ps0.05). Bone event cumulative incidence was 4 times greater in subjects who suffered from chronic GVHD.Assessment of phalangeal QUS in young BMT survivors points towards impairment of bone status and endocrine dysfunction and chronic GVHD as risk factors of adverse bone events.

Context: Hesx1 is one of the earliest homeodomain transcription factors expressed during pituitary development. Very few HESX1 mutations have been identified in humans; although in those cases the disease phenotype shows considerable variability, all but one of the patients display an ectopic posterior pituitary and/or optic nerve abnormalities.Objective: The objectives of the study were to describe the complex phenotype associated with the panhypopituitarism of two unrelated Italian patients who, at birth, presented with hypoglycemic seizures and respiratory distress complicated by shock, in a familial context of neonatal death in one family and spontaneous miscarriage in both families and to identify the molecular basis of this unusual syndrome.Main Outcome Measures: Magnetic resonance imaging of the pituitary region, study of HESX1 gene and transcripts, and assessment of the ability of mutated HESX1 proteins to repress transcription were measured.Results: Magnetic resonance imaging examination showed an anterior pituitary aplasia in a flat sella turcica and a normally located posterior pituitary in both patients. A constellation of extrapituitary developmental defects were found in the two patients, but without any optic nerve abnormalities. Sequencing of HESX1 exons and their flanking intronic regions revealed two different homozygous mutations. A frameshift (c.449_450delAC) was identified in one case, whereas the other patient carried a splice defect (c.357 + 2T>C) confirmed by the study of HESX1 transcripts. If translated, these mutations would lead to the synthesis of truncated proteins partly or entirely lacking the homeodomain, with no transcriptional repression, as shown by their inability to inhibit PROP1 activity.Conclusions: These observations reveal two novel HESX1 mutations in a so-far-undescribed disease phenotype characterized by a life-threatening neonatal condition associated with anterior pituitary aplasia, in the absence of ectopic posterior pituitary and optic nerve abnormalities, two features classically associated with HESX1 defects.

Summary Objectives Autoimmune targeting of hypothalamic-neurohypophyseal structures in children and young adults with posterior pituitary and anterior pituitary dysfunction, as well as pituitary stalk involvement, are not yet completely understood. Design We aimed to (1) evaluate the presence of circulating vasopressin-cell autoantibodies (AVPc-Abs) in young patients with central diabetes insipidus (CDI), (2) detect organ-specific autoantibodies as markers of autoimmunity, and (3) define the relationship between immune markers and neuroimaging findings. Patients Tw enty patients were evaluated at a median age of 16·3 years. Tw elve patients had idiopathic CDI, six had Langerhans cell histiocytosis (LCH) and two had germinoma. AVPc-Abs were evaluated in 40 healthy children. Magnetic resonance imaging (MRI) of the hypothalamic-pituitary region was performed longitudinally in all subjects. Measurements Circulating arginine vasopressin (AVP), protein tyrosine phosphatase (IA2), glutamic acid decarboxylase (GAD), 21-hydroxylase (21-OH), endomysium antibodies (EMA), parietal cell (PCA), thyroid peroxidase (TPO), thyroglobulin (TG) and TSHreceptor (TSHr) autoantibodies were evaluated. Results Circulating AVPc-Abs were found in 15 patients (75%), nine with idiopathic CDI, four with LCH and two with germinoma; the pituitary stalk was involved in most of them. Five patients with idiopathic CDI showed a persistence of AVPc-Abs during follow-up and one became positive subsequently. Serum IA2 autoantibodies were demonstrated in 14 patients (70%) and 21-OH autoantibodies in three of them. Conclusion In idiopathic CDI, circulating AVPc-Abs suggest an autoimmune involvement of the neurohypophyseal system. The identification of AVPc-Abs in subjects who could have either idiopathic CDI or LCH or germinoma, however, indicates that AVPc-Abs cannot be considered a completely reliable marker of autoimmune CDI. Thus, close clinical and MRI follow-up are needed because AVPc-Abs may mask germinoma or LCH.

Objective: A consensus exists that severe growth hormone deficiency (GHD) in adults is defined by a peak GH response to insulin-induced hypoglycemia (insulin tolerance test, ITT) of less than 3 μg/l based on a cohort of subjects with a mean age of 45 years. Design and methods: By considering one of the following two criteria for the diagnosis of probable permanent GHD, i.e. the severity of GHD (suggested by the presence of multiple pituitary hormone deficiencies (MPHD)) or the magnetic resonance (MR) imaging identification of structural hypothalamic–pituitary abnormalities, 26 patients (17 males, 9 females, mean age 20.8±2.3 years, range 17–25 years) were selected for re-evaluation of the GH response to ITT and their IGF-I concentration. Eight subjects had isolated GHD (IGHD) and 18 had MPHD. Normative data for peak GH were obtained after ITT in 39 healthy subjects (mean age 21.2±4.4 years, range 15.1–30.0 years) and the reference range for IGF-I was calculated using normative data from 117 healthy individuals. Results: Mean peak GH response to ITT was significantly lower in the 26 patients (1.8±2.0 μg/l, range 0.1–6.1 μg/l) compared with the 39 controls (18.5±15.5 μg/l, range 6.1–84.0 μg/l; P < 0.0001). One subject with septo-optic dysplasia had a peak GH response of 6.1 μg/l that overlapped the lowest peak GH response obtained in normal subjects. There was an overlap for IGF-I SDS between subjects with IGHD and MPHD, as well as with normal controls. The diagnostic accuracy of a peak GH response of 6.1 μg/l showed a 96% sensitivity with 100% specificity. The maximum diagnostic accuracy with IGF-I SDS was obtained with a cut-off of −1.7 SDS (sensitivity 77%, specificity 100%) while an IGF-I ≤ − 2.0 SDS showed a sensitivity of 62%. Conclusion: Our data show that the cut-off value of the peak GH response to ITT of less than 3 μg/l or 5 μg/l and of IGF-I of less than −2.0 SDS are too restrictive for the diagnosis of permanent GH deficiency in the transition period. We suggest that permanent GHD could be investigated more accurately by means of an integrated analysis of clinical history, the presence of MPHD, IGF-I concentration and the MR imaging findings of structural hypothalamic–pituitary abnormalities.

The analysis of locomotion in laboratory animals plays a crucial role in many scientific research areas. In fact, important information on animals’ behavior and their reaction to a particular stimulus is deduced from a careful analysis of their movements. The techniques commonly adopted to support such analysis have many limitations, which make the related systems particularly ineffective. On the one hand, the human observation and annotation process is strongly observer-dependent and expensive in terms of time and efforts. On the other hand, the use of more sophisticated systems based on video recordings and recognition algorithms is very expensive and complex. In order to face this challenge, this paper presents a tracking solution based on passive Radio Frequency Identification (RFID) technology in Ultra High Frequency (UHF) band, allowing the tracking of laboratory animals with a high accuracy. The overall solution consists of a hybrid system including hardware and software components. In particular, in this paper, the attention is focused on the software component as the hardware has already been described in previous works. The software component is a Web-oriented solution that offers a complete 2D and 3D information tool including reports, dashboards, and tracking graphs. The proposed solution was widely tested using twelve laboratory mice and compared with an automated video-tracking software (i.e., EthoVision) in order to demonstrate its effectiveness and reliability. The obtained results have demonstrated that the proposed solution is able to correctly detect and reconstruct the events occurring in the animals’ cage, and to offer a complete and user-friendly tool to support researchers in behavioral analysis of small laboratory animals.