Abnormal methylation at the KvDMR1 imprinting control region in clinically normal children conceived by assisted reproductive technologies

Genomic imprinting alterations have been shown to be associated with assisted reproductive technologies (ARTs) in animals. At present, data obtained in humans are inconclusive; however, some epidemiological studies have demonstrated an increased incidence of imprinting disorders in children conceived by ARTs. In the present study, we focused on the effect of ARTs [IVF and intracytoplasmic sperm injection (ICSI)] on the epigenetic reprogramming of the maternally methylated imprinting control region KvDMR1 in clinically normal children. Qualitative and quantitative methylation at KvDMR1 were assessed by the methylation-specific PCR approach and by the methylation-sensitive enzymatic digestion associated with real-time PCR method, respectively. DNA was obtained from peripheral blood of 12/18 and umbilical cord blood and placenta of 6/18 children conceived by IVF or ICSI. The methylation patterns observed in this group were compared with the patterns observed in 30 clinically normal naturally conceived children (negative controls) and in 3 naturally conceived Beckwith-Wiedemann syndrome patients (positive controls). Hypomethylation at KvDMR1 was observed in 3/18 clinically normal children conceived by ARTs (2 conceived by IVF and 1 by ICSI). A discordant methylation pattern was observed in the three corresponding dizygotic twins. Our findings corroborate the hypothesis of vulnerability of maternal imprinting to ARTs. Furthermore, the discordant methylation at KvDMR1 observed between dizygotic twins could be consequent to one of the following possibilities: (i) a differential vulnerability of maternal imprints among different embryos; or (ii) epimutations that occurred during gametogenesis resulting in the production of oocytes without the correct primary imprint at KvDMR1.

Fear of heights: cognitive performance and postural control

Fear of heights, or acrophobia, is one of the most frequent subtypes of specific phobia frequently associated to depression and other anxiety disorders. Previous evidence suggests a correlation between acrophobia and abnormalities in balance control, particularly involving the use of visual information to keep postural stability. This study investigates the hypotheses that (1) abnormalities in balance control are more frequent in individuals with acrophobia even when not exposed to heights, that (2) acrophobic symptoms are associated to abnormalities in visual perception of movement; and that (3) individuals with acrophobia are more sensitive to balance-cognition interactions. Thirty-one individuals with specific phobia of heights and thirty one non-phobic controls were compared using dynamic posturography and a manual tracking task. Acrophobics had poorer performance in both tasks, especially when carried out simultaneously. Previously described interference between posture control and cognitive activity seems to play a major role in these individuals. The presence of physiologic abnormalities is compatible with the hypothesis of a non-associative acquisition of fear of heights, i.e., not associated to previous traumatic events or other learning experiences. Clinically, this preliminary study corroborates the hypothesis that vestibular physical therapy can be particularly useful in treating individuals with fear of heights.

Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics

Context Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulatioin in BD. Objective: To use tract-based spatial statistics (TBSS) to examine VVM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Design: Cross-sectional, case-control, whole-brain DTI using TBSS. Setting: University research institute. Participants: Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type 1 (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Main Outcome Measures: Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Results: Subjects with BD vs controls had significantly greater FA (t > 3.0, P <=.05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P <=.05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P <.01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P <.01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. Conclusions: To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

Association of EGFR c.2073A > T polymorphism with decreased risk of diffusely infiltrating astrocytoma in a Brazilian case-control study

Epidermal growth factor receptor (EGFR) gene overexpression has been implicated in the development of many types of tumors, including glioblastomas, the most frequent diffusely infiltrating astrocytomas. However, little is known about the influence of the polymorphisms of EGFR on EGFR production and/or activity, possibly modulating the susceptibility to astrocytomas. This study aimed to examine the association of two EGFR promoter polymorphisms (c.-191C > A and c.-216G > T) and the c.2073A > T polymorphism located in exon 16 with susceptibility to astrocytomas, EGFR gene expression and survival in a case-control study of 193 astrocytoma patients and 200 cancer-free controls. We found that the variant TT genotype of the EGFR c.2073A > T polymorphism was associated with a significantly decreased risk of astrocytoma when compared with the AA genotype [sex- and age-adjusted odds ratio 0.51, 95% confidence interval 0.26-0.98]. No association of the two promoter EGFR polymorphisms (or combinations of these polymorphisms) and risk of astrocytomas, EGFR expression or survival was found. Our findings suggest that modulation of the EGFR c.2073A > T polymorphism could play a role in future therapeutic approaches to astrocytoma. (Int J Biol Markers 2008; 23: 140-6)

Glissonian approach for laparoscopic mesohepatectomy

Experience with advanced techniques has increased the indications for laparoscopic liver resection. This video demonstrates technical aspects of a pure laparoscopic mesohepatectomy using intrahepatic Glissonian technique. To the best of our knowledge, this is the first case of anatomic laparoscopic mesohepatectomy using the Glissonian approach published in the English literature. A 62-year-old man with colorectal liver metastasis occupying central liver segments was referred for surgical treatment. The first step is the control of segment 4 pedicle. Using the round ligament as a guide, one incision is performed on its right margin and another is made at the bottom of segment 4. A vascular clamp is introduced through those incisions to occlude segment 4 Glissonian sheath. The next step is to control the right anterior pedicle. The first incision is made in front of the hilum and another is performed on the right edge of gallbladder bed. Laparoscopic clamp is introduced through these incisions and closed producing ischemic discoloration of segments 5 and 8. Vascular clamp is replaced by an endoscopic vascular stapling device and stapler is fired. Line of liver transection is marked along the liver surface following ischemic area. Liver transection is accomplished with bipolar vessel sealing device and endoscopic stapling device as appropriate. Specimen was extracted through a suprapubic incision. Liver raw surfaces were reviewed for bleeding and bile leaks. Operative time was 200 min with minimum blood loss and no need for blood transfusion. Recovery was uneventful, and the patient was discharged on the fifth postoperative day. Histological examination revealed clear surgical margins. Mesohepatectomy can be safely performed laparoscopically in selected patients and by surgeons with expertise in both liver surgery and laparoscopic techniques. The use of the intrahepatic Glissonian approach may help to identify the exact limits of the mesohepatectomy to avoid ischemic injury of the remnant liver.

Ultrasound features of carpal tunnel syndrome: a prospective case-control study

Purpose The purpose of the study was to examine the most adequate cut-off point for median nerve cross-sectional area and additional ultrasound features supporting the diagnosis of carpal tunnel syndrome (CTS). Material and methods Forty wrists from 31 CTS patients and 63 wrists from 37 asymptomatic volunteers were evaluated by ultrasound. All patients were women. The mean age was 49.1 years (range: 29-78) in the symptomatic and 45.1 years (range 24-82) in the asymptomatic group. Median nerve cross-sectional area was obtained using direct (DT) and indirect (IT) techniques. Median nerve echogenicity, mobility, flexor retinaculum measurement and the anteroposterior (AP) carpal tunnel distance were assessed. This study was IRB-approved and all patients gave informed consent prior to examination. Results In CTS the median nerve cross-sectional area was increased compared with the control group. Median nerve cross-sectional area of 10 mm(2) (DT) and 9 mm(2) (IT) had high sensitivity (85% and 88.5%, respectively), specificity (92.1% and 82.5%) and accuracy (89.3% and 82.5%) in the diagnosis of CTS. CTS patients had an increased carpal tunnel AP diameter, flexor retinaculum thickening, reduced median nerve mobility and decreased median nerve echogenicity. Conclusion Ultrasound assists in the diagnosis of CTS using the median nerve diameter cut-off point of 10 mm(2) (DT) and 9 mm(2) (IT) and several additional findings.

Novel potential therapies for septic shock

Sepsis is the systemic inflammatory response syndrome secondary to a local infection. Septic shock, the severe complication of sepsis associated with refractory hypotension, is frequently a near-fatal condition requiring prompt diagnosis and management. Although the recent years have been associated with considerable improvements in the knowledge of the pathophysiology of the disease and remarkable advances have been achieved in sepsis treatment, the morbidity and mortality of this disease are still unacceptably high. In this review, we will briefly discuss the ongoing standard treatment of septic shock and describe novel potential therapies, aiming to improve hemodynamic support and/or control inflammatory response in sepsis. These therapies were associated with benefits in experimental studies and have been tested or are currently under testing in randomized controlled studies with septic patients.

Evaluation of the influence of different types of seats on postural control in individuals with paraplegia

Study design: Cross-sectional study. Objectives: To assess the importance of proprioceptive and vision information on different types of wheelchair seats with regard to postural control in paraplegic individuals during static posture. Setting: Centre of Rehabilitation at the University Hospital/FMRP-USP and Rehabilitation Outpatient Clinic at University Hospital/UNICAMP, Brazil. Methods: This study involved 11 individuals with paraplegia. All individuals were submitted to an evaluation of static balance with their eyes open and closed in three different types of seats: wheelchair seat, foam seat and gel seat. Balance evaluation was performed by using the Polhemus system, in which body displacements and anteroposterior and mediolateral speeds were assessed in a static seated position in the different types of seats. Data were analyzed using analysis of variance. The differences were considered at P<0.05. Results: No statistical differences were found between the three types of seats in terms of displacements and anteroposterior and mediolateral speeds, or between seats with individuals keeping their eyes open or closed (P>0.05). However, it was observed that body displacements were more prominent toward an anteroposterior than a mediolateral direction. Conclusion: This study suggests that individuals with paraplegia tend to exhibit a more anteroposterior body displacement than a mediolateral one, with no significant differences between the types of seats in both situations of eyes open and closed. Spinal Cord (2010) 48, 825-827; doi:10.1038/sc.2010.30; published online 30 March 2010

Major histocompatibility complex (MHC) class II but not MHC class I molecules are required for efficient control of Strongyloides venezuelensis infection in mice

P>Strongyloides stercoralis is an intestinal nematode capable of chronic, persistent infection and hyperinfection of the host; this can lead to dissemination, mainly in immunosuppressive states, in which the infection can become severe and result in the death of the host. In this study, we investigated the immune response against Strongyloides venezuelensis infection in major histocompatibility complex (MHC) class I or class II deficient mice. We found that MHC II(-/-) animals were more susceptible to S. venezuelensis infection as a result of the presence of an elevated number of eggs in the faeces and a delay in the elimination of adult worms compared with wild-type (WT) and MHC I(-/-) mice. Histopathological analysis revealed that MHC II(-/-) mice had a mild inflammatory infiltration in the small intestine with a reduction in tissue eosinophilia. These mice also presented a significantly lower frequency of eosinophils and mononuclear cells in the blood, together with reduced T helper type 2 (Th2) cytokines in small intestine homogenates and sera compared with WT and MHC I(-/-) animals. Additionally, levels of parasite-specific immunoglobulin M (IgM), IgA, IgE, total IgG and IgG1 were also significantly reduced in the sera of MHC II(-/-) infected mice, while a non-significant increase in the level of IgG2a was found in comparison to WT or MHC I(-/-) infected mice. Together, these data demonstrate that expression of MHC class II but not class I molecules is required to induce a predominantly Th2 response and to achieve efficient control of S. venezuelensis infection in mice.