Gender-based differences in the clustering of metabolic syndrome factors in children and adolescents

We depicted gender-differences in metabolic syndrome (MS) clustering before and after puberty in pediatrics, in order to develop gender specific preventive strategies for childhood obesity. We considered 1079 children and adolescents (529 females and 550 males; mean age 11.5 \ub1 2.8 year). According to body mass index (BMI) percentiles the subjects were classified as normal weight BMI <75th, overweight BMI 75-95th and with obesity BMI >95th. MS was diagnosed when three of the following criteria for age and sex percentiles were met: BMI >95th, triglycerides (TGs) level >95th, high-density lipoprotein-cholesterol (HDL-c) level <5th, blood pressure (blood pressure) >95th percentile, fasting blood glucose (FBG) >100 mg/dL and/or homeostatic model assessment-insulin resistance (HOMA-IR) >97.5th percentile. The prevalence of dismetabolic factors was similar in both genders, except for pathological BP, which was higher in males (p = 0.02). MS was detected only in patients with obesity, with a higher prevalence in pubertal than late/post-pubertal subjects (p < 0.001), without any significant difference between gender. In pre-puberty, the most common MS combination was obesity (HBMI) + hypertension (HBP) + hyperglycemia/insulin resistance (HGLY/IR) followed by HBMI + low HDL-levels (LHDL) + HGLY/IR versus HBMI + HBP + HGLY/IR followed by HBMI + HBP + LHDL, respectively, in females and males. In the early and late/post-pubertal periods, the most prevalent combination remained similar to pre-puberty, additionally in both sexes other combinations, such as HBMI + HTG + HBP + HGLY/IR, HBMI + HBP + LHDL + HGLY/IR, HBMI + HTG + LHDL + HGLY/IR and HBMI + HTG + LHDL + HBP + HGLY/IR were also detected, differently distributed in males and females. We confirm that MS is an important consequence related to obesity, particularly in the post-puberty stage. Some gender-based differences should be considered early in order to identify specific preventive and treatment strategies

The cooling of atomic and molecular gas in DR21

We present an overview of a high-mass star formation region through the major (sub-)mm, and far-infrared cooling lines to gain insight into the physical conditions and the energy budget of the molecular cloud. We used the KOSMA 3m telescope to map the core ($10'\times 14'$) of the Galactic star forming region DR 21/DR 21 (OH) in the Cygnus X region in the two fine structure lines of atomic carbon CI and four mid-$J$ transitions of CO and $^{13}$CO, and CS J=7\TO6. These observations have been combined with FCRAO J=1\TO0 observations of $^{13}$CO and C$^{18}$O. Five positions, including DR21, DR21 (OH), and DR21 FIR1, were observed with the ISO/LWS grating spectrometer in the \OI 63 and 145 $\mu$m lines, the \CII 158 $\mu$m line, and four high-$J$ CO lines. We discuss the intensities and line ratios at these positions and apply Local Thermal Equilibrium (LTE) and non-LTE analysis methods in order to derive physical parameters such as masses, densities and temperatures. The CO line emission has been modeled up to J=20. From non-LTE modeling of the low- to high-$J$ CO lines we identify two gas components, a cold one at temperatures of T_\RM{kin}\sim 30-40 K, and one with T_\RM{kin}\sim 80-150 K at a local clump density of about n(H$_2$)$\sim 10^4-10^6$ cm$^{-3}$. While the cold quiescent component is massive containing typically more than 94 % of the mass, the warm, dense, and turbulent gas is dominated by mid- and high-$J$ CO line emission and its large line widths. The medium must be clumpy with a volume-filling of a few percent. The CO lines are found to be important for the cooling of the cold molecular gas, e.g. at DR21 (OH). Near the outflow of the UV-heated source DR21, the gas cooling is dominated by line emission of atomic oxygen and of CO

Chronic myelogenous leukemia with acquired c-kit activating mutation and transient bone marrow mastocytosis

Mutations of the c-kit gene have been reported in myeloproliferative disorders. We describe here a case of Ph + (b2a2) chronic myelogenous leukemia that, during the course of disease, showed an unusual bone marrow mast-cell infiltration. A mutational screening for the c-kit gene, performed on DNA routinely cryopreserved during the follow-up, evidenced the D816Y-activating mutation as an additional genetic abnormality. Treatment with imatinib mesylate resulted in a substantial decrease of the BCR-ABL/ABL ratio and in the absence of c-kit mutation. It is likely that the superimposed c-kit mutation, in this case, may account for the transient bone marrow mastocytosis

Music benefits on postoperative distress and pain in pediatric day care surgery

Postoperative effect of music listening has not been established in pediatric age. Response on postoperative distress and pain in pediatric day care surgery has been evaluated. Forty-two children were enrolled. Patients were randomly assigned to the music-group (music intervention during awakening period) or the non-music group (standard postoperative care). Slow and fast classical music and pauses were recorded and played via ambient speakers. Heart rate, blood pressure, oxygen saturation, glucose and cortisol levels, faces pain scale and Face, Legs, Activity, Cry, Consolability (FLACC) Pain Scale were considered as indicators of response to stress and pain experience. Music during awakening induced lower increase of systolic and diastolic blood pressure levels. The non-music group showed progressive increasing values of glycemia; in music-group the curve of glycemia presented a plateau pattern (P<0.001). Positive impact on reactions to pain was noted using the FLACC scale. Music improves cardiovascular parameters, stress-induced hyperglycemia. Amelioration on pain perception is more evident in older children. Positive effects seems to be achieved by the alternation of fast, slow rhythms and pauses even in pediatric age

Cryptic subtelomeric translocation t(2;16)(q37;q24) segregating in a family with unexplained stillbirths and a dysmorphic, slightly retarded child

We here describe a submicroscopic translocation affecting the subtelomeric regions of chromosomes 2q and 16q and segregating in a family with stillbirths, early pregnancy losses, and two dysmorphic and slightly retarded babies. FISH analysis showed a 46,XY,der(2)t(2,16)(q37.3;q24.3) in the propositus, and a balanced t(2;16) in his mother, her conceptus and maternal grandfather. FISH with YACs and BACs made it possible to map the 2q37 breakpoint precisely between the regions covered by y952E1 and y746H1, and the 16q breakpoint between the regions encompassed by bA 309g16 and bA 533d19. The contribution of 2q37.3 monosomy and 16q24.3 trisomy to the proband's phenotype is compared with that in reported patients with similar imbalances of either chromosome

FISH characterization of t(8;12)(q12;p13) observed as the sole karyotypic anomaly in a myelodysplastic syndrome patient

We report a t(8;12)(q12; p13) as the sole cytogenetic anomaly in a patient with a myelodysplastic syndrome (MDS). By means of FISH, we mapped the genomic region involved in the breakpoint (bkp) on both chromosomes. The 12p13 bkp mapped between markers WI-664 and WI-9218, immediately distal to the breakpoint cluster region frequently involved in hematological neoplasms targeted by y964C10. The 8q12 bkp (not yet investigated by FISH) was characterized and found to occur between markers WI-3263 and D8S524 within the region recognized by y874E1

Expanding the phenotype associated to KMT2A variants: overlapping clinical signs between Wiedemann–Steiner and Rubinstein–Taybi syndromes

Lysine-specific methyltransferase 2A (KMT2A) is responsible for methylation of histone H3 (K4H3me) and contributes to chromatin remodeling, acting as \u201cwriter\u201d of the epigenetic machinery. Mutations in KMT2A were first reported in Wiedemann\u2013Steiner syndrome (WDSTS). More recently, KMT2A variants have been described in probands with a specific clinical diagnosis comprised in the so-called chromatinopathies. Such conditions, including WDSTS, are a group of overlapping disorders caused by mutations in genes coding for the epigenetic machinery. Among them, Rubinstein\u2013Taybi syndrome (RSTS) is mainly caused by heterozygous pathogenic variants in CREBBP or EP300. In this work, we used next generation sequencing (either by custom-made panel or by whole exome) to identify alternative causative genes in individuals with a RSTS-like phenotype negative to CREBBP and EP300 mutational screening. In six patients we identified different novel unreported variants in KMT2A gene. The identified variants are de novo in at least four out of six tested individuals and all of them display some typical RSTS phenotypic features but also WDSTS specific signs. This study reinforces the concept that germline variants affecting the epigenetic machinery lead to a shared molecular effect (alteration of the chromatin state) determining superimposable clinical conditions

Detection of chromosome aberrations in metaphase and interphase tumor cells by in situ hybridization using chromosome-specific library probes

Chromosome aberrations in two glioma cell lines were analyzed using biotinylated DNA library probes that specifically decorate chromosomes 1, 4, 7, 18 and 22 from pter to qter. Numerical changes, deletions and rearrangements of these chromosomes were radily visualized in metaphase spreads, as well as in early prophase and interphase nuclei. Complete chromosomes, deleted chromosomes and segments of translocated chromosomes were rapidly delineated in very complex karyotypes. Simultaneous hybridizations with additional subregional probes were used to further define aberrant chromosomes. Digital image analysis was used to quantitate the total complement of specific chromosomal DNAs in individual metaphase and interphase cells of each cell line. In spite of the fact that both glioma lines have been passaged in vitro for many years, an under-representation of chromosome 22 and an over-representation of chromosome 7 (specifically 7p) were observed. These observations agree with previous studies on gliomas. In addition, sequences of chromosome 4 were also found to be under-represented, especially in TC 593. These analyses indicate the power of these methods for pinpointing chromosome segments that are altered in specific types of tumors

A Single-Molecule Bioelectronic Portable Array for Early Diagnosis of Pancreatic Cancer Precursors

A cohort of 47 patients is screened for pancreatic cancer precursors with a portable 96-well bioelectronic sensing-array for single-molecule assay in cysts fluid and blood plasma, deployable at point-of-care (POC). Pancreatic cancer precursors are mucinous cysts diagnosed with a sensitivity of at most 80% by state-of-the-art cytopathological molecular analyses (e.g., KRASmut DNA). Adding the simultaneous assay of proteins related to malignant transformation (e.g., MUC1 and CD55) is deemed essential to enhance diagnostic accuracy. The bioelectronic array proposed here, based on single-molecule-with-a-large-transistor (SiMoT) technology, can assay both nucleic acids and proteins at the single-molecule limit-of-identification (LOI) (1% of false-positives and false-negatives). It comprises an enzyme-linked immunosorbent assay (ELISA)-like 8 × 12-array organic-electronics disposable cartridge with an electrolyte-gated organic transistor sensor array, and a reusable reader, integrating a custom Si-IC chip, operating via software installed on a USB-connected smart device. The cartridge is complemented by a 3D-printed sensing gate cover plate. KRASmut, MUC1, and CD55 biomarkers either in plasma or cysts-fluid from 5 to 6 patients at a time, are multiplexed at single-molecule LOI in 1.5 h. The pancreatic cancer precursors are classified via a machine-learning analysis resulting in at least 96% diagnostic-sensitivity and 100% diagnostic-specificity. This preliminary study opens the way to POC liquid-biopsy-based early diagnosis of pancreatic-cancer precursors in plasma