The Impact of Sex Chromosome Trisomies (XXX, XXY, XYY) on Early Social Cognition: Social Orienting, Joint Attention, and Theory of Mind.

OBJECTIVE: About 1:650-1,000 children are born with an extra X or Y chromosome (XXX; XXY; XYY), which results in a sex chromosome trisomy (SCT). This study aims to cross-sectionally investigate the impact of SCT on early social cognitive skills. Basic orienting toward social cues, joint attention, and theory of mind (ToM) in young children with SCT were evaluated. METHOD: About 105 children with SCT (range: 1-7 years old) were included in this study, as well as 96 age-matched nonclinical controls. Eyetracking paradigms were used to investigate the eye gaze patterns indicative of joint attention skills and orienting to social interactions. The ToM abilities were measured using the subtest ToM of the Developmental NEuroPSYchological Assessment, second edition, neuropsychological test battery. Recruitment and assessment took place in the Netherlands and in the United States. RESULTS: Eyetracking results revealed difficulties in children with SCT in social orienting. These difficulties were more pronounced in children aged 3 years and older, and in boys with 47,XYY. Difficulties in joint attention were found over all age groups and karyotypes. Children with SCT showed impairments in ToM (26.3% in the [well] below expected level), increasing with age. These impairments did not differ between karyotypes. CONCLUSIONS: An impact of SCT on social cognitive abilities was found already at an early age, indicating the need for early monitoring and support of early social cognition. Future research should explore the longitudinal trajectories of social development in order to evaluate the predictive relationships between social cognition and outcome later in life in terms of social functioning and the risk for psychopathology.

Metformin as targeted treatment in fragile X syndrome.

BACKGROUND: Individuals with fragile X syndrome (FXS) have both behavioral and medical comorbidities and the latter include obesity in approximately 30% and the Prader-Willi Phenotype (PWP) characterized by severe hyperphagia and morbid obesity in less than 10%. Metformin is a drug used in individuals with type 2 diabetes, obesity or impaired glucose tolerance and it has a strong safety profile in children and adults. Recently published studies in the Drosophila model and the knock out mouse model of FXS treated with metformin demonstrate the rescue of multiple phenotypes of FXS. MATERIALS AND METHODS: We present 7 cases of individuals with FXS who have been treated with metformin clinically. One case with type 2 diabetes, 3 cases with the PWP, 2 adults with obesity and/or behavioral problems and, a young child with FXS. These individuals were clinically treated with metformin and monitored for behavioral changes with the Aberrant Behavior Checklist and metabolic changes with a fasting glucose and HgbA1c. RESULTS: We found consistent improvements in irritability, social responsiveness, hyperactivity, and social avoidance, in addition to comments from the family regarding improvements in language and conversational skills. No significant side-effects were noted and most patients with obesity lost weight. CONCLUSION: We recommend a controlled trial of metformin in those with FXS. Metformin appears to be an effective treatment of obesity including those with the PWP in FXS. Our study suggests that metformin may also be a targeted treatment for improving behavior and language in children and adults with FXS.

The challenge of non-union in subtrochanteric fractures with breakage of intramedullary nail: evaluation of outcomes in surgery revision with angled blade plate and allograft bone strut.

PURPOSE: Subtrochanteric fractures have a bimodal age distribution. They usually require open reduction and internal fixation. Closed reduction and intramedullary nail fixation rate are increased for this type of fracture. As a result, the hardware breakage and non-union rate is high among such patients. Our purpose is to evaluate the outcomes of the role of blade plate and bone strut allograft in the management of subtrochanteric non-union by femoral nailing. MATERIALS AND METHODS: We reported a group of 22 patients with subtrochanteric non-union, associated with breakage of the intramedullary nail with medial femoral allograft bone and lateral blade plate and wire (PS) s; and a group of 13 patients with subtrochanteric non-union, associated with breakage of the intramedullary nail treated with lateral blade plate and screws (CG). The chosen criteria to evaluate the two group during the clinical and radiological follow-up were the quality of life, measured by The Short Form (12) Health Survey (SF-12), the hip function and quality of life related to it, measured by the Harris Hip Score (HHS), bone healing, measured by Radiographic Union Score (RUS) by XR and CT at 1 year after the surgery, and postoperative complications. The evaluation endpoint was set at 12 months. RESULTS: The Bone healing measured by RUS occurred and also the full recovery before the first trauma measured by SF-12 and HHS are better in PS group. We only had three unimportant complications in PS while four breakage hardware in CG. CONCLUSION: We conclude that in complicated non-unions, the use of blade plate and bone strut allograft has a definite positive role in the management of such cases.

The treatment of distal third humeral diaphyseal fractures: Is there still a place for the external fixation?

INTRODUCTION: The treatment for humeral diaphyseal fractures is still controversial. The purpose of this study was to evaluate the clinical and radiographic outcomes of treating humeral distal third diaphyseal fractures by using external fixation technique. MATERIALS AND METHODS: We retrospectively review 65 cases of diaphyseal humeral fractures (31 type A, 23 type B and 11 type C of the AO/OTA classification) treated with external fixation (Orthofix FAD small) between 2008 and 2013. The mean follow-up was 48 months (24-72 months). There were 12 open fractures; however, no cases of concomitant vascular injury were described. The transolecranic traction was always applied to promote partial reduction through ligamentotaxis. In case of interposition of soft tissues impeding reduction, a small incision was performed allowing mobilization of bone ends. RESULTS: All fractures resulted healed at a mean of 11 weeks (range 9-13 weeks); the average time of removal of the external fixator was 88 days (range 65-95 days). At the last follow-up, the mean elbow flexion was 132.6° (Min 126°-Max 137°) and the mean elbow extension was 6.4° (Max 0°-Min 13°). The Cassebaum's index rated as excellent in 47.8 % (31 patients), good in 37 % (24 patients), fair in 9.2 % (6 patients) and poor in 6 % (4 patients). The mean DASH score at the final follow-up was 14.7 (range 0-33); 15 patients had a range score between 10 and 20, 43 had less than 10, and seven had more than 20. We observed three cases of superficial infections and two cases of acute radial nerve palsy recovered within 3 months. CONCLUSION: According to the excellent clinical results and full rate of consolidation, we state external fixation as a valid option in the treatment of distal third humeral diaphyseal fractures.

Behavioral phenotypes in males with XYY and possible role of increased NLGN4Y expression in autism features.

The male sex chromosome disorder, 47,XYY syndrome (XYY), is associated with increased risk for social-emotional difficulties, attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). We hypothesize that increased Y chromosome gene copy number in XYY leads to overexpression of Y-linked genes related to brain development and function, thereby increasing risk for these phenotypes. We measured expression in blood of two Y genes NLGN4Y and RPS4Y in 26 boys with XYY and 11 male controls and evaluated whether NLGN4Y expression correlates with anxiety, ADHD, depression and autistic behaviors (from questionnaires) in boys with XYY. The XYY cohort had increased risk of ASD behaviors on the social responsiveness scale (SRS) and increased attention deficits on the Conners' DSM-IV inattention and hyperactive scales. In contrast, there was no increase in reported symptoms of anxiety or depression by the XYY group. Peripheral expression of two Y genes in boys with XYY vs. typically developing controls was increased twofold in the XYY group. Results from the SRS total and autistic mannerisms scales, but not from the attention, anxiety or depression measures, correlated with peripheral expression of NLGN4Y in boys with XYY. Males with XYY have social phenotypes that include increased risk for autism-related behaviors and ADHD. Expression of NLGN4Y, a gene that may be involved in synaptic function, is increased in boys with XYY, and the level of expression correlates with overall social responsiveness and autism symptoms. Thus, further investigation of NLGN4Y as a plausible ASD risk gene in XYY is warranted.

Micromotion in the fracture healing of closed distal metaphyseal tibial fractures: A multicentre prospective study.

The dynamic locking screw (DLS) in association with minimally invasive plate osteosynthesis (MIPO) in a bridging construct for simple metadiaphyseal long bone fractures enables modulation of the rigidity of the system and facilitates the development of early and triplanar bone callus. Twenty patients affected by distal tibial fracture were treated with MIPO bridging technique and DLS at the proximal side of the fracture. Time of consolidation, quality of the reduction, complications and American Orthopaedic Foot and Ankle Society (AOFAS) score were monitored and the results compared with those from a control group treated with only standard screws on both fracture sides. Student t-test for independent samples was used for the comparison of means between the two groups. Chi-square test was used for the comparison of proportions. A multiple logistic regression model was constructed to assess the possible confounding effects. Performance was considered significant for p<0.05. The mean healing time was 17.6 ± 2.8 weeks in the group treated with standard screws and 13.5 ± 1.8 weeks in the group treated with DLS (t=5.5, p<0.0001). The DLS was associated with early healing and triplanar bone callus.

Heel displaced intra-articular fractures treated with mini-calcaneal external fixator.

INTRODUCTION: Treatment of displaced heel fractures is controversial; however, ORIF is widely described in the literature to be the gold-standard. Percutaneous reduction and monolateral external fixation is gaining increasing attention because it provides a good and stable reduction, and minimises soft tissue complications due to open surgery, such as deep infections and delays in wound healing. The aim of this study was to show that the new Orthofix Calcaneal Minifixator (six pins) provides a greater stability than the four-pin version to enable a better and more stable reduction, an earlier weight-bearing (30 days) and improved functional outcomes. METHODS: A series of 69 consecutive closed heel intraarticular displaced fractures treated with the new Orthofix Calcaneal Minifixator were evaluated. Patients were assessed clinically with the Maryland Foot Score and radiologically with standard radiographs. RESULTS: The clinical results at follow-up were excellent in 37 cases (53.6%), good in 27 (39.2%), fair in two (2.9%) and poor in three (4.3%). The mean preoperative Böhler's angle was 5.2˚ (range 0-18˚) and the mean postoperative value was 28.5˚ (range 16-38˚). CONCLUSION: The excellent functional outcomes were despite some radiological images of imperfect posterior facet anatomical reduction and seemed to correlate with the use of a good and stable minimally-invasive surgical technique. This technique enabled early weight-bearing, minimised complications, respected the delicate biology of this anatomical site and restored the good heel volume and Böhler angle.

Unconsummated marriage: can it still be considered a consequence of vaginismus?

Unconsummated marriage (UM) is the failure to perform successful sexual intercourse at the beginning of the marriage. Vaginismus has been traditionally reported as the leading cause. ED is also a leading cause for UM. This appears to be a significant problem in the conservative middle-Eastern societies and in the developing countries, where couples are strongly prevented by religious rules and cultural taboos from sexual experiences before wedding. One could think that according to major sexual freedom and information, in Western countries UM is now disappearing, but the number of observed cases by the authors in 2008-2012 was relevant. The aim of this study is to compare the literature data from non-Western countries with the features of UM in Western ones, focusing on cases observed by the authors, and to verify whether the etiology of UM proposed in the '70s is still relevant, outlining any changes that occur in current reality. In our series, traditional appearance of UM is no more effective, while the role of man is undervalued, because of his frailty, lack of self-confidence and ignorance, expressing a social and cultural change of man's role in the couple.

Laparoscopic partial nephrectomy for endophytic hilar tumors: feasibility and outcomes.

OBJECTIVE: To analyze feasibility and outcomes of laparoscopic partial nephrectomy (LPN) for endophytic hilar tumors in low-intermediate (ASA I-II) risk patients. METHODS: This is a single centre retrospective study. From May 2009 to September 2011, 208 LPNs were performed at our institution. Overall 11 (5.2%) elective LPNs were for hilar tumors not visible on kidney surface. Hilar tumor was defined as a mass located in the renal hilum and in contact with a major renal vessel on preoperative imaging. Procedures were carried out by a single experienced surgeon (G.G.) via retroperitoneal approach by clamping the only main renal artery. RESULTS: Mean (range) age of patients was 45.3 years (38.2-64.1), tumor size 1.6 cm (1.2-2.0), warm ischemia time 24 min (19-32), operative time 140 min (110-200) and estimated blood loss 270 ml (100-750). Two collecting system injuries were observed and repaired intraoperatively. No conversion to open surgery was required. Final pathological examination revealed 10 renal cell carcinomas and 1 oncocytoma. A negative surgical margin was obtained in 10/11 (91%) patients. Renal function and serum hemoglobin were nearly unaltered pre and post-surgery. No tumor recurrence was observed at mean (range) follow-up of 34 months (15-43). CONCLUSIONS: In experienced hands, LPN represents a feasible, safe and effective treatment for selected patients diagnosed with endophytic hilar masses. A larger number of patients and longer follow-up are required to draw definitive conclusions.

Plication corporoplasty versus Nesbit operation for the correction of congenital penile curvature. A long-term follow-up.

BACKGROUND AND OBJECTIVES: Aim of the study is to evaluate the long-term results of tunica albuginea plication in patients with congenital curvature of the penis and to compare them with those obtained with the Nesbit technique. METHODS: Overall, 62 patients underwent surgical correction of congenital curvature of the penis from 2003 to 2008 at our institution. Of these, only 31 consented to be reevaluated. Nineteen patients had plication corporoplasty by means of one or more double crossed introflecting stitches (group A) while 12 patients had a traditional Nesbit technique with excision of small parts of tunica albuginea (group B). All patients were reevaluated with physical examination, a specific questionnaire and self-photography on erection, after a mean follow-up of 38 months in group A and 40 months in group B. Student's t test was employed for statistical analyses. RESULTS: A total of 3 recurrences of curvature were observed in group A, 1-3 months after surgery, which required surgical correction. In all three patients, reabsorbable sutures had been employed for albuginea plication. No recurrences were observed in group B (P = 0.15). A minimal persistent deviation was present in 6 patients in group A (31%) and in 6 patients in group B (50%) (P = 0.29). A minimal hyposensitivity of glans and prepuce was reported in 7 patients in group A (38%) and in 9 patients in group B (75%) (P = 0.03). CONCLUSIONS: Plication corporoplasty yields good and stable results when compared to the Nesbit technique provided that unabsorbable sutures are used and superficial scalpel incision of the albuginea is performed.

DNA sequences and proteic antigens of H. pylori in cholecystic bile and tissue of patients with gallstones.

BACKGROUND: Although Helicobacter pylori DNA sequences have been detected in cholecystic bile and tissue of patients with gallstones, controversial results are reported from different geographic areas. AIM: To detect H. pylori in cholecystic bile and tissue of patients with gallstones from a previously uninvestigated geographic area, southern Italy. Detection included both the bacterial DNA and the specific antigen (H. pylori stool antigen) identified in the stools of infected patients for diagnostic purposes. PATIENTS AND METHODS: The study enclosed 33 consecutive patients undergoing laparoscopic cholecystectomy for gallstones. DNA sequences of H. pylori were detected by polymerase chain reaction in both cholecystic bile and tissue homogenate. Moreover, we assayed H.pylori stool antigen on gall-bladder cytosolic and biliary proteins after their extraction. Bacterial presence in the stomach was assessed by urea breath test in all patients and Deltadelta13CPDB value assumed as marker of intragastric load. Fisher's exact probability and Student's t-tests were used for statistical analysis. RESULTS: DNA sequences of H. pylori in bile were found in 51.5% and significantly correlated with its presence in cholecystic tissue homogenate (P<0.005), H. pylori stool antigen in gall-bladder (P=0.0013) and bile (P=0.04) proteins, gastric infection (P<0.01) and intragastric bacterial load (P<0.001). No correlation was found, however, with sex and age of the patients. CONCLUSIONS: Our prevalence value of bacterial DNA in bile and gall-bladder of patients with gallstones agreed with that of the only other Italian study. The simultaneous presence of both bacterial DNA and proteic antigen suggests that the same prototype of bacterium could be located at both intestinal and cholecystic level and, therefore, the intestine represents the source of biliary contagion.

Genetic and clinical characterization of patients with an interstitial duplication 15q11-q13, emphasizing behavioral phenotype and response to treatment.

The clinical significance of an interstitial duplication of (15)(q11-q13) remains unclear and controversial. The reported phenotypes vary widely and appear to be influenced by the parent of origin of the duplication. Aside from cases of dup(15) reported with autism, the behavioral phenotype of individuals with dup(15) has not been described. We present three families, two with intrachromosomal duplication (15)(q11-q13) ascertained because of developmental delay in a relative. Two families show clear evidence of multigenerational maternal inheritance. The individuals discussed in this paper have minor anomalies and developmental delays. In addition, we describe a behavioral phenotype which often includes attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder. Responses to medications used to manage these behaviors are also described, including a positive response to methylphenidate and a poor response to fluoxetine. The duplication in each presenting individual, and available family members, was investigated utilizing cytogenetic and molecular techniques including high resolution cytogenetics, fluorescence in situ hybridization (FISH), DNA methylation studies, and quantitative fluorescence PCR. High resolution cytogenetic techniques alone missed some cases, demonstrating the need to confirm results with other methods.

[Papillary carcinoma of the thyroglossal duct cyst: a case report]. / Il carcinoma papillifero della cisti del dotto tireoglosso: caso clinico.

The thyroglossal duct cyst is the most common anomaly in thyroid development. To date, approximately 250 cases have been reported, the majority being papillary thyroid carcinomas. In most cases the diagnosis is established only after excision of a clinically benign thyroglossal duct cyst. Controversies exist in relation to a rational and effective therapeutic approach. A further case of thyroglossal duct papillary carcinoma affecting a 52 years-old man is presented to highlight the clinicopathological features of this condition. FNAC resulted false negative. Surgery consisted in a Sistrunk procedure, followed by total thyroidectomy and central lymphectomy after definitive histological diagnosis. In view of the prolonged course of papillary carcinoma, long-term follow-up is mandatory.

Protein synthesis-dependent and -independent regulation of hippocampal synapses by brain-derived neurotrophic factor.

A fundamental difference between short-term and long-term forms of synaptic plasticity is the dependence on transcription and translation of new genes. Using organotypic cultures of hippocampal slices, we have investigated whether the modulation of synapses by brain-derived neurotrophic factor (BDNF) also requires protein synthesis. Long-term treatment of hippocampal slice cultures with BDNF increased the number of docked vesicles, but not that of reserve pool vesicles, at CA1 excitatory synapses. BDNF also increased the levels of the vesicle proteins synaptophysin, synaptobrevin, and synaptotagmin, without affecting the presynaptic membrane proteins syntaxin and SNAP-25, or the vesicle-binding protein synapsin-I. The increase in synaptophysin and synaptobrevin expression was moderate (2-fold) and occurred within 6 h after BDNF application. In contrast, synaptotagmin expression took 24 h to reach maximum levels (5-fold). The delayed increase in synaptotagmin was blocked by protein synthesis inhibitors, while the early increase in synaptophysin and synaptobrevin was not. Moreover, the BDNF-induced increase of synaptotagmin was blocked by inhibiting the cAMP/protein kinase A (PKA) pathway. However, BDNF did not activate PKA, and application of a PKA activator did not mimic the BDNF effect. Taken together, these results suggest a novel, protein synthesis-dependent form of BDNF modulation that requires cAMP gating.

Signaling mechanisms mediating BDNF modulation of synaptic plasticity in the hippocampus.

Although recent studies indicate that brain-derived neurotrophic factor (BDNF) plays an important role in hippocampal synaptic plasticity, the underlying signaling mechanisms remain largely unknown. Here, we have characterized the signaling events that mediate the BDNF modulation of high-frequency synaptic transmission. Mitogen-associated protein kinase (MAPK), phosphotidylinositol-3 kinase (PI3K), and phospholipase C-gamma (PLC-gamma) are the three signaling pathways known to mediate neurotrophin signaling in other systems. In neonatal hippocampal slices, application of BDNF rapidly activated MAPK and PI3K but not PLC-gamma. BDNF greatly attenuated synaptic fatigue at CA1 synapses induced by a train of high-frequency, tetanic stimulation (HFS). Inhibition of the MAPK and PI3K, but not PLC-gamma, prevented the BDNF modulation of high-frequency synaptic transmission. Neurotrophin-3 (NT-3), a close relative of BDNF, did not activate MAPK or PI3K and had no effect on synaptic fatigue in the neonatal hippocampus. Neither forskolin, which activated MAPK but not PI3 kinase, nor ciliary neurotrophic factor (CNTF), which activated PI3K but not MAPK, affected HFS-induced synaptic fatigue. Treatment of the slices with forskolin together with CNTF still had no effect on synaptic fatigue. Thus, although the activation of MAPK and PI3K is required, the two together are not sufficient to mediate the BDNF effect. Inhibition of new protein synthesis by anisomycin or cycloheximide did not prevent the BDNF effect. These data suggest that BDNF modulation of high-frequency transmission is independent of protein synthesis but requires MAPK and PI3K and yet another signaling pathway to act together in the hippocampus.

Vagal paraganglia bind biotinylated interleukin-1 receptor antagonist: a possible mechanism for immune-to-brain communication.

Interleukin-1 beta is a proinflammatory cytokine released by activated immune cells. In addition to orchestrating immune responses to infection, interleukin-1 beta is a key mediator of immune-to-brain communication. Interleukin-1 beta and endotoxin (which releases IL1 beta from immune cells) cause centrally mediated illness responses such as fever, aphagia, etc. These effects are blocked by intraperitoneal IL1 receptor antagonist (IL1ra), suggesting critical involvement of peripheral IL1 receptors. Centrally mediated illness responses are also blocked by vagotomy, suggesting that IL1 beta directly or indirectly activates vagal afferents. To test for IL1 beta binding whole vagus (abdominal, laryngeal, and thoracic) and sections of hepatic vagus and liver hilus were incubated with biotinylated IL1ra and processed for avidin-biotin complex (ABC) or avidin-FITC histochemistry. Glomus cells of vagal paraganglia were labeled in all regions of the vagus. Biotinylated IL1ra also labeled smooth muscle and endothelial cells of blood vessels and lymphoid tissues. No label was present in omission or competition controls. These data suggest that centrally mediated illness responses result from IL1 activation of vagal paraganglia.

Blockade of cytokine induced conditioned taste aversion by subdiaphragmatic vagotomy: further evidence for vagal mediation of immune-brain communication.

Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are cytokines released by activated immune cells. IL-1 beta and TNF-alpha elicit various illness symptoms including avoidance of novel tastes with which they have been paired (conditioned taste aversion). Previous hypotheses to account for these actions have focused on blood-borne IL-1 beta and TNF-alpha exerting their effects directly at the brain. However, recent evidence suggests that these cytokines may activate subdiaphragmatic vagal afferents. The present experiments demonstrate that subdiaphragmatic vagal transection both attenuates acquisition and facilitates extinction of conditioned taste aversions induced by i.p. administration of either IL-1 beta or TNF-alpha.

Blockade of interleukin-1 induced hyperthermia by subdiaphragmatic vagotomy: evidence for vagal mediation of immune-brain communication.

Interleukin-1 beta (IL-1 beta), a cytokine released by activated immune cells, elicits various illness symptoms including hyperthermia. Previous hypotheses to account for these actions have focused on blood-borne IL-1 beta exerting its effects directly at the level of the brain. However, recent behavioral and physiological evidence suggest that IL-1 beta can activate the subdiaphragmatic vagus. The present experiments demonstrate that subdiaphragmatic vagal transection disrupts the hyperthermia-inducing effects of recombinant human IL-1 beta and stress. These data provide evidence for a novel route of immune-brain communication, as well as a novel route whereby stress can influence physiological processes.

Ionospheric effects on the transmission of ultralow-frequency plasma waves.

Measurements of magnetospheric ultralow-frequency plasma waves (period tau, approximately 18 to 150 seconds) on the ground under continuous daylight conditions in the Antarctic and under alternate day-night solar illumination at the conjugate station in Quebec indicate a significant local time dependence in the transmission properties of the ionosphere for waves of these periods. When the Antarctic station is compared with the Quebec station, the tilt (with respect to the ionosphere) of the orientation plane of the waves is observed to be larger at local noon than at local night.