Type 2 diabetes remission 2 years post Roux-en-Y gastric bypass and sleeve gastrectomy: the role of the weight loss and comparison of DiaRem and DiaBetter scores.

AIMS: The comparative efficacy of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear. The DiaRem diabetes remission prediction score uses HbA1c , age and diabetes medications but not diabetes duration. The aim of this study was to compare the DiaRem with the DiaBetter score that includes diabetes duration, upon combined (complete plus partial) 2-year post-surgery diabetes remission in people following RYGB and sleeve gastrectomy, and to investigate the relationship between weight loss and diabetes remission. METHODS: A retrospective single-centre cohort study of obese people with diabetes who underwent RYGB (107) or sleeve gastrectomy (103) and a validation cohort study (173) were undertaken. Diabetes remission, % weight loss, DiaRem, DiaBetter scores and areas under receiving operator characteristic (ROC) curves were calculated. The relationship between % weight loss and diabetes remission was investigated using logistic regression. RESULTS: The proportion of people achieving diabetes remission was highest for those with the lowest DiaBetter and DiaRem scores. Areas under the ROC curves were comparable [DiaBetter: 0.867 (95%CI: 0.817-0.916); DiaRem: 0.865 (95%CI: 0.814-0.915), P=0.856]. Two-year % weight loss was higher post RYGB [26.6 (95%CI: 24.8-28.4)] vs post-sleeve gastrectomy [20.6 (95%CI: 18.3-22.8), P<0.001]. RYGB had 151% higher odds of diabetes remission [OR 2.51 (95%CI: 1.12-5.60), P=0.025]. This association became non-significant when adjusted for % weight loss. CONCLUSION: DiaBetter and DiaRem scores predict diabetes remission following both procedures. Two-year % weight loss plays a key role in determining diabetes remission.

Analysis of the Candida albicans Phosphoproteome.

Candida albicans is an important human fungal pathogen in both immunocompetent and immunocompromised individuals. C. albicans regulation has been studied in many contexts, including morphological transitions, mating competence, biofilm formation, stress resistance, and cell wall synthesis. Analysis of kinase- and phosphatase-deficient mutants has made it clear that protein phosphorylation plays an important role in the regulation of these pathways. In this study, to further our understanding of phosphorylation in C. albicans regulation, we performed a deep analysis of the phosphoproteome in C. albicans. We identified 19,590 unique peptides that corresponded to 15,906 unique phosphosites on 2,896 proteins. The ratios of serine, threonine, and tyrosine phosphosites were 80.01%, 18.11%, and 1.81%, respectively. The majority of proteins (2,111) contained at least two detected phosphorylation sites. Consistent with findings in other fungi, cytoskeletal proteins were among the most highly phosphorylated proteins, and there were differences in Gene Ontology (GO) terms for proteins with serine and threonine versus tyrosine phosphorylation sites. This large-scale analysis identified phosphosites in protein components of Mediator, an important transcriptional coregulatory protein complex. A targeted analysis of the phosphosites in Mediator complex proteins confirmed the large-scale studies, and further in vitro assays identified a subset of these phosphorylations that were catalyzed by Cdk8 (Ssn3), a kinase within the Mediator complex. These data represent the deepest single analysis of a fungal phosphoproteome and lay the groundwork for future analyses of the C. albicans phosphoproteome and specific phosphoproteins.

Iron status in obesity: An independent association with metabolic parameters and effect of weight loss.

BACKGROUND AND AIMS: Growing evidence has shown that ferritin concentrations are associated with obesity and insulin resistance, and with nonalcoholic fatty liver disease. However, it is unclear whether ferritin is simply an inflammatory marker, or it may directly contribute to the pathogenesis of obesity-related metabolic alterations. The aim of our study was to investigate the independent associations of ferritin levels with metabolic parameters in overweight/obese subjects before and after hypocaloric diet-induced weight changes. METHODS AND RESULTS: A sample study of 48 premenopausal, 39 postmenopausal women and 50 men was retrospectively analyzed. Clinical, bioimpedentiometry and biochemical data from baseline evaluations and after 3, 6 and 12 months of hypocaloric diet were collected. In the whole sample study, the baseline values of ferritin concentrations were positively correlated with body mass index (BMI) (r = 0.21, p < 0.05) and mass body fat (MBF) (r = 0.26, p < 0.05), whereas the serum iron level was negatively correlated with MBF (r = -0.29, p < 0.05). In premenopausal women, BMI-adjusted ferritin concentrations were negatively associated with high-density lipoprotein-cholesterol and positively related with triglycerides and aspartate aminotransferase. Moreover, the quantitative ferritin reduction at 12 months was positively associated with the relative reduction of BMI (r = 0.34, p < 0.05). Finally, the association between changes of alanine aminotransferase and ferritin levels at 12 months from baseline turned out to be independent of respective BMI changes (ß = 0.31, p < 0.05). CONCLUSION: In obesity, ferritin, putatively entailing increased iron storage, is independently associated with lipid derangements and transaminase levels, and the association with the latter persists after weight changes.

Effects of whole body vibration plus diet on insulin-resistance in middle-aged obese subjects.

We investigated the early effects of whole body vibration (WBV) added to hypocaloric diet on insulin-resistance and other parameters associated with glucose regulation in sedentary obese individuals. We randomly assigned 34 patients to WBV plus hypocaloric diet (WBV group) or diet alone (CON group) for 8 weeks. Fasting and post-load glucose, insulin, lipids, C-reactive protein, tumor necrosis factor-α, leptin, adiponectin were assessed. Insulin sensitivity index (ISI) was derived from oral-glucose-tolerance test. Body composition was evaluated with dual-energy X-ray absorptiometry. Both groups lost approximately 5% of weight, with greater reduction of body fat in WBV than in CON (-7.1±1.2 Kg vs. -5.3±1.0 Kg, p=0.003). Percent variation of ISI was more pronounced in WBV than in CON group (+35±4% vs. + 22±5%, p=0.002), accompanied by slight improvement in post-load glucose (-1.07±0.02 vs. - 0.12±0.01 mmol/l, p=0.031) but without changes in fasting levels. Adiponectin significantly increased in WBV group compared with CON (p=0.021 for comparison) whereas no differences in leptin and inflammatory markers were observed. In middle-aged sedentary obese subjects, WBV added to hypocaloric diet for 8 weeks improved body composition, insulin-resistance, glucose regulation and adiponectin levels to a greater extent compared with diet alone. Efficacy and feasibility of this approach in the long term need to be ascertained.

Genetic inactivation of Kcnj16 identifies Kir5.1 as an important determinant of neuronal PCO2/pH sensitivity.

The molecular identity of ion channels which confer PCO(2)/pH sensitivity in the brain is unclear. Heteromeric Kir4.1/Kir5.1 channels are highly sensitive to inhibition by intracellular pH and are widely expressed in several brainstem nuclei involved in cardiorespiratory control, including the locus coeruleus. This has therefore led to a proposed role for these channels in neuronal CO(2) chemosensitivity. To examine this, we generated mutant mice lacking the Kir5.1 (Kcnj16) gene. We show that although locus coeruleus neurons from Kcnj16((+/+)) mice rapidly respond to cytoplasmic alkalinization and acidification, those from Kcnj16((-/-)) mice display a dramatically reduced and delayed response. These results identify Kir5.1 as an important determinant of PCO(2)/pH sensitivity in locus coeruleus neurons and suggest that Kir5.1 may be involved in the response to hypercapnic acidosis.

Infection and immunity for human parvovirus B19 in patients with febrile exanthema.

The contribution of parvovirus B19 (B19V) as a causative agent of febrile exanthema (FE) in Cordoba, Argentina, was analysed by detection of viral DNA, and specific IgM and IgG. Serum from 141 patients with FE who were negative for measles and rubella, collected during 2005-2009, plus serum from 31 healthy individuals, were assayed. B19V was the aetiological agent in 14·9% of all FE cases, and in 39·1% in an epidemic year (2007). B19V DNA was detected in 47·6% of IgM-positive FE patients, 30·2% of IgM-negative/IgG-positive FE patients, and 9·7% of healthy controls, indicating B19V long-term infection in ~10% of immunocompetent individuals. Persistent B19V DNA was significantly more frequent in children than adults and in males than females. All patients with acute B19V infection had rash and fever, 85·7% had adenopathy, and only 14·3% had arthropathy. This is the first follow-up study of markers of infection and immunity for B19V infection in Argentina.

Atopic dermatitis (AD) management in an Italian pediatric clinic.

AIM: Atopic dermatitis (AD) is a common, chronic relapsing inflammatory skin disease characterized by dry skin and variable pruritus sometimes associated with allergic disease in other organs as asthma and rhinoconjunctivitis. AD affects deeply the Quality of Life, thus can be extremely disabling and may cause psychological problems for both affected children and their families. METHODS: In order to investigate the estimated prevalence of the disease and the beliefs of the Italian pediatricians, a group of 437 Italian family pediatricians covering a population of almost 380000 children participated in a study based on a questionnaire of 38 items. RESULTS: According to answers of the participants, the incidence of AD has been estimated around 10% of the population and food allergy is believed to be the trigger of the acute phase of the disease in infants. As a second opinion, dermatologists are consulted more frequently than allergologists. CONCLUSION: The use of emollients is advised in general whilst topical corticosteroids treatment is prescribed only in selected cases; more than 50% of pediatricians do not prescribe topical calcineurin inhibitors.

Single-incision laparoscopic right hemicolectomy (Br J Surg 2010; 97: 1881-1883).

The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website (http://www.bjs.co.uk). All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length.

A NOTES approach for thoracic surgery: transgastric thoracoscopy via a diaphragmatic incision in a survival porcine model.

AIM: Recently the NOTES approach has been extended to mediastinum by a transesophageal access and to the thorax by a transvescical endoscopic approach. The aim of this study was to assess the feasibility and the safety of transgastric endoscopic approach to the thoracic cavity, with lung biopsy, in a survival porcine model. METHODS: The study was performed on four 20-30 kg female pigs (Sus scrofus domesticus). Following gastric wall incision, the muscular pars of the left diaphragmatic dome was incised along with the parietal pleura and the endoscope advanced into the thoracic cavity. In all animals, a thoracoscopy was performed as well as peripheral lung biopsy. At the end of the operation the endoscope was withdrawn from the thoracic cavity after pleural sac decompression and the diaphragmatic incision closed by endoscopic clips under maximal expansion of lungs. The gastric incision was finally closed by endoscopic clips. Chest-tube placement was not utilized. Animals were sacrificed by day 15 postoperatively. RESULTS: The gastroscope was easily introduced into the thoracic cavity that allowed to visualize the pleural cavity and to perform simple surgical procedures such as lung biopsies without complications. There were neither respiratory distress episodes nor surgical complications to report. No adverse event occurred during the survival period. The postmortem examination 15 days after surgery revealed a good closure of the diaphragmatic incision. At necropsy, the lung biopsies were completely healed. There were no signs of infection in both thoracic and peritoneal cavities. The length of follow-up and number of animals studied might have not been sufficient. CONCLUSION: This study demonstrates the feasibility of transgastric thoracoscopy in porcine model. Long-term follow-up of much larger series will be necessary for provision of more reliable answers if this approach should be adopted in the future and eventually translated for humans with advantages for patients.

A novel KCNA1 mutation identified in an Italian family affected by episodic ataxia type 1.

Episodic ataxia type 1 (EA1) is a rare human neurological syndrome characterized by continuous myokymia and attacks of generalized ataxia that can be triggered by abrupt movements, emotional stress and fatigue. An Italian family has been identified where related members displayed continuous myokymia, episodes of ataxia, attacks characterized by myokymia only, and neuromyotonia. A novel missense mutation (F414C), in the C-terminal region of the K(+) channel Kv1.1, was identified in the affected individuals. The mutant homotetrameric channels were non-functional in Xenopus laevis oocytes. In addition, heteromeric channels resulting from the co-expression of wild-type Kv1.1 and Kv1.1(F414C), or wild-type Kv1.2 and Kv1.1(F414C) subunits displayed reduced current amplitudes and altered gating properties. This indicates that the pathogenic effect of this KCNA1 mutation is likely to be related to the defective functional properties we have identified.

Increased release and activity of matrix metalloproteinase-9 in patients with mandibuloacral dysplasia type A, a rare premature ageing syndrome.

Mandibuloacral dysplasia type A (MADA; OMIM 248370), a rare disorder caused by mutation in the LMNA gene, is characterized by post-natal growth retardation, craniofacial and skeletal anomalies (mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of cranial sutures, low bone mass and joint contractures), cutaneous changes and partial lipodystrophy. Little is known about the molecular mechanisms by which LMNA mutations produce bone alterations. An altered bone extracellular matrix (ECM) remodelling could play a pivotal role in this disorder and influence part of the typical bone phenotype observed in patients. Therefore, we have focused our investigation on matrix metalloproteinases (MMPs), which are degradative enzymes involved in ECM degradation and ECM remodelling, thus likely contributing to the altered bone mineral density and bone metabolism values seen in five MADA patients. We evaluated the serum levels of several MMPs involved in bone development, remodelling and homeostasis, such as MMP-9, -2, -3, -8 and -13, and found that only the 82 kDa active enzyme forms of MMP-9 are significantly higher in MADA sera compared with healthy controls (n = 16). The serum level of MMP-3 was instead lower in all patients. No significant differences were observed between controls and MADA patients for the serum levels of MMP-2, -8 and -13 and of tissue inhibitor of metalloproteinase 2, a natural inhibitor of MMP-9. Similarly, normal serum levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-6 and IL-1beta were detected. These data suggest a possible involvement of MMP-9 in MADA disease, underlying the potential use in diagnosis and therapy.

Cost-effectiveness of bariatric surgery in adolescents with severe obesity in the UK.

Evidence shows that surgery for severe obesity in adults improves health and psychological functioning, and is cost-effective. Data on bariatric surgery for adolescents with severe obesity are extremely limited, with no evidence on cost-effectiveness. We evaluated the lifetime cost-effectiveness of bariatric surgery compared with no surgery in adolescents with severe obesity from the UK's National Health Service perspective. Eighteen adolescents with body mass index ≥40 kg m-2 who underwent bariatric surgery (laparoscopic Roux en Y Gastric Bypass [RYGB] [N = 9], and laparoscopic Sleeve Gastrectomy [SG] [N = 9]) at University College London Hospitals between January 2008 and December 2013 were included. We used a Markov cohort model to compare the lifetime expected costs and quality-adjusted life years (QALYs) between bariatric surgery and no surgery. Mean cost of RYGB and SG procedures were £7100 and £7312, respectively. For RYGB vs. no surgery, the incremental cost/QALY was £2018 (95% CI £1942 - £2042) for males and £2005 (95% CI £1974 - £2031) for females. For SG vs. no surgery, the incremental cost/QALY was £1978 (95% CI £1954 - £2002) for males and £1941 (95% CI £1915 - £1969) for females. Bariatric surgery in adolescents with severe obesity is cost-effective; it is more costly than no surgery however it markedly improved quality of life.

Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) by rosiglitazone suppresses components of the insulin-like growth factor regulatory system in vitro and in vivo.

Rosiglitazone (Rosi) belongs to the class of thiazolidinediones (TZDs) that are ligands for peroxisome proliferator-activated receptor gamma (PPARgamma). Stimulation of PPARgamma suppresses bone formation and enhances marrow adipogenesis. We hypothesized that activation of PPARgamma down-regulates components of the IGF regulatory system, leading to impaired osteoblast function. Rosi treatment (1 microm) of a marrow stromal cell line (UAMS-33) transfected with empty vector (U-33/c) or with PPARgamma2 (U-33/gamma2) were analyzed by microarray. Rosi reduced IGF-I, IGF-II, IGFBP-4, and the type I and II IGF receptor (IGF1R and IGF2R) expression at 72 h in U-33/gamma2 compared with U-33/c cells (P < 0.01); these findings were confirmed by RT-PCR. Rosi reduced secreted IGF-I from U-33/gamma2 cells by 75% (P < 0.05). Primary marrow stromal cells (MSCs) extracted from adult (8 months) and old (24 months) C57BL/6J (B6) mice were treated with Rosi (1 microm) for 48 h. IGF-I, IGFBP-4, and IGF1R transcripts were reduced in Rosi-treated MSCs compared with vehicle (P < 0.01) and secreted IGF-I was also suppressed (P < 0.05). B6 mice treated with Rosi (20 mg/kg.d) for short duration (i.e. 4 d), and long term (i.e. 7 wk) had reduced serum IGF-I; this was accompanied by markedly suppressed IGF-I transcripts in the liver and peripheral fat of treated animals. To determine whether Rosi affected circulating IGF-I in humans, we measured serum IGF-I, IGFBP-2, and IGFBP-3 at four time points in 50 postmenopausal women randomized to either Rosi (8 mg/d) or placebo. Rosi-treated subjects had significantly lower IGF-I at 8 wk than baseline (-25%, P < 0.05), and at 16 wk their levels were reduced 14% vs. placebo (P = 0.15). We conclude that Rosi suppresses IGF-I expression in bone and liver; these changes could affect skeletal acquisition through endocrine and paracrine pathways.

Regulation by fasting of rat insulin-like growth factor I and its receptor. Effects on gene expression and binding.

We have examined, in liver and extrahepatic tissues, the effects of fasting on total insulin-like growth factor I (IGF-I) mRNA levels, on levels of different IGF-I mRNAs generated by alternative splicing of the primary IGF-I transcript, and on IGF-I receptor binding and mRNA levels. A 48-h fast decreased total IGF-I mRNA levels by approximately 80% in lung and liver, approximately 60% in kidney and muscle, and only approximately 30-40% in stomach, brain, and testes. In heart, IGF-I mRNA levels did not change. The levels of the different splicing variants, however, were essentially coordinately regulated within a given tissue. Specific 125I-IGF-I binding in lung, testes, stomach, kidney, and heart was increased by fasting by approximately 30-100%, whereas in brain 125I-IGF-I binding did not change in response to fasting. In tissues in which fasting increased IGF-I receptor number, receptor mRNA levels increased approximately 1.6- to 2.5-fold, whereas when IGF-I receptor number was unchanged in response to fasting, receptor mRNA levels did not change. These data demonstrate that the change in IGF-I and IGF-I receptor mRNA levels during fasting is quantitatively different in different tissues and suggest that regulation of IGF-I and IGF-I receptor gene expression by fasting is discoordinate.

The growth-stimulatory effect of simian virus 40 T antigen requires the interaction of insulinlike growth factor 1 with its receptor.

We have used a plasmid expressing a temperature-sensitive (ts) mutant of simian virus 40 (SV40) T antigen, stably transfected into 3T3 cells, to study the role of insulinlike growth factor 1 (IGF-1) and its receptor in T-antigen-mediated growth. While 3T3 cells do not grow in serum-free medium, in 1% serum, or with the sole addition of either platelet-derived growth factor (PDGF) or IGF-1, cells expressing the tsA T antigen (BALB 58 cells) grow at 34 degrees C in either PDGF or 1% serum but not in IGF-1. At the restrictive temperature (39.6 degrees C), these cells can only grow in 10% serum. We show that BALB 58 cells, at 34 degrees C, have a markedly increased expression of IGF-1 and IGF-1 mRNA and that their growth in 1% serum (at 34 degrees C) is inhibited by an antisense oligodeoxynucleotide to the IGF-1 receptor RNA. When this tsA plasmid is stably transfected into cells constitutively overexpressing the human IGF-1 receptor cDNA, the resulting cell lines show a constitutively phosphorylated IGF-1 receptor and grow in serum-free medium at 34 degrees C (but not at 39.6 degrees C). A functional SV40 T antigen also increases the expression of a plasmid in which the reporter luciferase gene is under the control of a rat IGF-1 promoter. We conclude (i) that the SV40 T antigen induces the expression of IGF-1 and IGF-1 mRNA, at least in part by a transcriptional mechanism, thus altering the growth factors requirements, and (ii) that, in BALB/c3t3 cells, the SV40 T antigen necessitates a functional IGF-1 receptor for its growth-stimulating effect in low serum (or PDGF).

[Prevalence of anti-rubella and anti-parvovirus B19 antibodies in pregnant women in the city of Córdoba, and in women of fertile age in the city of Villa Mercedes, province of San Luis]. / Prevalencia de anticuerpos antirrubéola y antiparvovirus B19 en embarazadas de la ciudad de Córdoba y en mujeres en edad fértil de la ciudad de Villa Mercedes, San Luis.

We determined the prevalence of anti-rubella antibodies in 100 serum samples from pregnant women who attended routine examination at a private institution in the city of Córdoba, and in 100 serum samples from women of gestational age, 42 of whom were pregnant, attending health centres in the city of Villa Mercedes, province of San Luis. IgG antibodies against parvovirus 819 were also determined in the serum samples from Córdoba. Using the hemmagglutination inhibition test, we found a 98% prevalence of anti-rubella antibodies among pregnant women in Córdoba and of 96% among the women in Villa Mercedes, whereas the prevalence of anti-parvovirus 819 was 66% in the serum samples from Cordoba. These results coincide with those reported for other cities in the world, and establish an interest in continuing similar studies in order to monitor the immunization plan, which in Argentina has been going on since 1997. They also suggest the importance of the determination of IgM anti-parvovirus B19 in pregnant women who are symptomatic but with a negative result for rubella.

Active Subjects With Autoimmune Type 1 Diabetes Have Better Metabolic Profiles Than Sedentary Controls.

Previous studies in humans with type 1 diabetes mellitus (T1D) and in nonobese diabetic mice have investigated the beneficial immunomodulatory potential of aerobic physical activity. Performing high volume of aerobic exercise may favorably regulate autoimmunity in diabetes. We tested whether increased physical activity is a self-sufficient positive factor in T1D subjects. During a 3-month observational period, active (six males; 40.5 ± 6.1 years; BMI: 24.5 ± 2.1) and sedentary (four males, three females; 35.9 ± 8.9 years; BMI: 25.7 ± 3.8) T1D individuals on insulin pump therapy were studied for metabolic, inflammatory, and autoimmune parameters. At baseline and at the end of a 3-month period, glycosylated hemoglobin (HbA1c), autoantibodies (anti-GAD, anti-ZnT8, anti-IA2, and ICA) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. During the third month of the period, physically active T1D patients showed a significant reduction in the average glucose levels (-9%, p = 0.025, by CGM) compared to the first month values, and even their hyperglycemic episodes (>180 mg/dl) diminished significantly (-24.2%, p = 0.032 vs. first month). Moreover, active T1D subjects exhibited an improved body composition with respect to sedentary controls. No significant changes were detected as to the autoimmune and inflammatory profiles. This study confirms the beneficial role of physical exercise associated with insulin pump therapy in order to improve metabolic control in individuals with T1D. These preliminary positive observations need to be challenged in a prolonged interventional follow-up.

Congenic mice provide in vivo evidence for a genetic locus that modulates serum insulin-like growth factor-I and bone acquisition.

We identified quantitative trait loci (QTL) that determined the genetic variance in serum IGF-I through genome-wide scanning of mice derived from C57BL/6J(B6) x C3H/HeJ(C3H) intercrosses. One QTL (Igf1s2), on mouse chromosome 10 (Chr10), produces a 15% increase in serum IGF-I in B6C3 F2 mice carrying c3 alleles at that position. We constructed a congenic mouse, B6.C3H-10 (10T), by backcrossing c3 alleles from this 57-Mb region into B6 for 10 generations. 10T mice have higher serum and skeletal IGF-I, greater trabecular bone volume fraction, more trabeculae, and a higher number of osteoclasts at 16 wk, compared with B6 (P < 0.05). Nested congenic sublines generated from further backcrossing of 10T allowed for recombination and produced four smaller sublines with significantly increased serum IGF-I at 16 wk (i.e. 10-4, 10-7, 10-10, and 10-13), compared with B6 (P < 0.0003), and three smaller sublines that showed no differences in IGF-I vs. age- and gender-matched B6 mice. Like 10T, the 10-4 nested sublines at 16 wk had higher femoral mineral (P < 0.0001) and greater trabecular connectivity density with significantly more trabeculae than B6 (P < 0.01). Thus, by comprehensive phenotyping, we were able to narrow the QTL to an 18.3-Mb region containing approximately 148 genes, including Igf1 and Elk-3(ETS domain protein). Allelic differences in the Igf1s2 QTL produce a phenotype characterized by increased serum IGF-I and greater peak bone density. Congenic mice establish proof of concept of shared genetic determinants for both circulating IGF-I and bone acquisition.

Effects of Factor XIII Deficiency on Thromboelastography. Thromboelastography with Calcium and Streptokinase Addition is more Sensitive than Solubility Tests.

BACKGROUND: Homozygous or double heterozygous factor XIII (FXIII) deficiency is characterized by soft tissue hematomas, intracranial and delayed spontaneous bleeding. Alterations of thromboelastography (TEG) parameters in these patients have been reported. The aim of the study was to show results of TEG, TEG Lysis (Lys 60) induced by subthreshold concentrations of streptokinase (SK), and to compare them to the clot solubility studies results in samples of a 1-year-old girl with homozygous or double heterozygous FXIII deficiency. CASE: A year one girl with a history of bleeding from the umbilical cord. During her first year of life, several hematomas appeared in soft upper limb tissue after punctures for vaccination and a gluteal hematoma. One additional sample of a heterozygous patient and three samples of acquired FXIII deficiency were also evaluated. MATERIALS AND METHODS: Clotting tests, von Willebrand factor (vWF) antigen and activity, plasma FXIII-A subunit (pFXIII-A) were measured by an immunoturbidimetric assay in a photo-optical coagulometer. Solubility tests were performed with Ca(2+)-5 M urea and thrombin-2% acetic acid. Basal and post-FXIII concentrate infusion samples were studied. TEG was performed with CaCl2 or CaCl2 + SK (3.2 U/mL) in a Thromboelastograph. RESULTS: Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, fibrinogen, factor VIIIc, vWF, and platelet aggregation were normal. Antigenic pFXIII-A subunit was < 2%. TEG, evaluated at diagnosis and post FXIII concentrate infusion (pFXIII-A= 37%), presented a normal reaction time (R), 8 min, prolonged k (14 and 11min respectively), a low Maximum-Amplitude (MA) ( 39 and 52 mm respectively), and Clot Lysis (Lys60) slightly increased (23 and 30% respectively). In the sample at diagnosis, clot solubility was abnormal, 50 and 45 min with Ca-Urea and thrombin-acetic acid, respectively, but normal (>16 hours) 1-day post-FXIII infusion. Analysis of FXIII deficient and normal plasma mixtures (< 2-102% of pFXIII-A), showed that Ca-urea solubility was abnormal at pFXIII-A < 9%, thrombin-acetic acid at pFXIII-A<18%, but TEG MA and elasticity at 23% and Lys60 with SK at pFXIII-A< 40%. CONCLUSIONS: TEG parameters MA and elasticity, and Lys 60 in TEG either with Ca(2+) or Ca(2+) and SK are more sensitive to low levels of pFXIII than solubility tests. The increased Lys60 induced by a subthreshold concentration of SK could probably reflect the clot characteristics "in vivo" in many patients with pFXIII levels between 5-40% and could be potentially considered as screening test.

Characterization of transient noise in Advanced LIGO relevant to gravitational wave signal GW150914.

On September 14, 2015, a gravitational wave signal from a coalescing black hole binary system was observed by the Advanced LIGO detectors. This paper describes the transient noise backgrounds used to determine the significance of the event (designated GW150914) and presents the results of investigations into potential correlated or uncorrelated sources of transient noise in the detectors around the time of the event. The detectors were operating nominally at the time of GW150914. We have ruled out environmental influences and non-Gaussian instrument noise at either LIGO detector as the cause of the observed gravitational wave signal.