A 6q14.1‐q15 microdeletion in a male patient with severe autistic disorder,lack of oral language,and dysmorphic features with concomitant presence of a maternally inherited Xp22.31 copy number gain

We report on a male patient with severe autistic disorder, lack of oral language, and dysmorphic features who carries a rare interstitial microdeletion of 4.96 Mb at chromosome 6q14.1‐q15. The patient also harbors a maternally inherited copy number gain of 1.69 Mb at chromosome Xp22.31, whose pathogenicity is under debate.     

Modulation of regulatory T-cell activity in combination with interleukin-12 increases hepatic tolerogenicity in woodchucks with chronic hepatitis B

Regulatory T cells (Treg) play a critical role in the modulation of immune responses to viral antigens in chronic viral hepatitis. Woodchucks (Marmota monax) infected with the woodchuck hepatitis virus (WHV) represent the best animal model for chronic hepatitis B virus (HBV) infection. Examination of intrahepatic and peripheral Treg in uninfected and WHV chronically infected woodchucks showed a significant increase of intrahepatic Treg numbers in chronically infected animals, whereas no differences were found in peripheral blood. In agreement with these data, higher expression levels of Forkhead box P3 (Foxp3), interleukin (IL)-10, transforming growth factor beta (TGF-β) were detected in the liver of chronic WHV carriers in comparison to uninfected animals. Furthermore, treatment of WHV-infected animals with an adenovirus encoding IL-12 failed to reduce viral load, a finding that was associated with lymphocyte unresponsiveness to IL-12 stimulation in vitro. We observed that TGF-β and Treg play a major role in the lack of lymphocyte response to IL-12 stimulation, as TGF-β inhibition and Treg depletion allowed recovery of T-cell responsiveness to this cytokine. Based on these results, woodchucks were treated with IL-12 in combination with a TGF-β inhibitory peptide or Treg depletion. However, no antiviral effect was achieved and, instead, an enhancement of the intrahepatic tolerogenic environment was observed. CONCLUSION: Our data show that TGF-β inhibition or Treg depletion had no added benefit over IL-12 therapy in chronic WHV infection. IL-12 immunostimulation induces a strong immunosuppressive reaction in the liver of chronic WHV carriers that counteracts the antiviral effect of the treatment.     

Opciones de tratamiento quirúrgico en la estenosis de uretra bulbar

ObjectiveTo review the outcome of bulbar urethroplasty using two stage surgical techniques.Material and methodsTwenty-two of the 35 patients studied corresponded to end-to-end urethroplasty (ATT) and 13 to dorsal onlay graft (DOG) in preputial skin or oral mucosa variants. Clinical outcome was considered a failure when postoperative surgery was needed or the uroflowmetry was less than 15 ml/s. The following variables were studied: age, previous surgery, number of urethrotomies and stricture length. The curves and log-rank Curves using the log-rank were elaborated for follow-up and comparison, with the Cox regression model for risk factors.ResultsMean follow-up was 40.02 months. Of all the cases. 85.71% were successful. Of these, 86.36% were in the ATT group and 84.61% in the DOG group. There were no significant differences in the comparative LR test based in stricture length, previous surgery between both group and individualized for each management. The Cox regression model showed a risk of failure in the technique for the elderly patients (OR 2.2), it not achieving statistical significance in the remaining variables.ConclusionsThe success rate achieved with the ATT technique is verified a gold standard option in short strictures. The DOG is shown as a valid option in long strictures in bulbar urethral in medium follow-up, using a oral mucosa or preputial onlay graft. More long-term follow-up must be performed with a greater number of patients to better evaluate these results.     

Is on‐demand treatment effective in patients with severe haemophilia?

Summary. On‐demand therapy enables stopping haemorrhages rapidly, reducing joint pain and restoring joint mobility, but does not prevent the beginning and subsequent development of haemophilic arthropathy. The main objective of this study was to identify the clinical and orthopaedic status of severe haemophilic patients with bleeding phenotype receiving on‐demand treatment in Spain. We conducted an epidemiological, observational, retrospective study, recruiting 167 patients from 36 centres (92% of them with haemophilia A), median age at enrolment of 35 years. Forty per cent of the patients received a combination of on‐demand and short‐term prophylaxis regimen; the rest was under on‐demand treatment. One hundred and forty‐five patients (87%) reported at least one bleeding episode and 22 (13%) of the biologically severe patients had no bleeding phenotype. Seventy‐one per cent of the studied population presented established haemophilic arthropathy, reaching 80% if we exclude patients without bleeding phenotype. Forty‐three per cent of these patients had one or two joints affected, 28% of them had three or four affected joints, 20% reported five or six affected joints and 9% more than six injured joints. An increase in established haemophilic arthropathy with age was observed. Forty‐six patients underwent orthopaedic surgery at least once. These data show that on‐demand therapy is not effective in preventing the development of haemophilic arthropathy in severe haemophilic population with bleeding phenotype. Therefore, we suggest that the optimal treatment in these patients should be based on prophylaxis. We recommend analysing the reasons for ending prophylaxis, in case its reinstatement should be necessary.     

Selective enamel etching: effect on marginal adaptation of self-etch LED-cured bond systems in aged Class I composite restorations

The aim of this study was to evaluate the influence of previous enamel etch and light emitting diode (LED) curing on gap formation of self-etch adhesive systems in Class I composite restorations after thermomechanical aging (TMA). Thus, on 192 human molars, a box-shaped Class I cavity was prepared maintaining enamel margins. Self-etch adhesives (Clearfil SE and Clearfil S3) were used to restore the preparation with a microhybrid composite. Before application of the adhesives, half of the teeth were enamel etched for 15 seconds with 37% phosphoric acid; the other half were not etched. For the photoactivation of the adhesives and composite, three light-curing units (LCUs) were used: one polywave (Ultra-Lume LED 5, UL) and two single-peak (FlashLite 1401, FL and Radii-cal, RD) LEDs. After this, epoxy resin replicas of the occlusal surface were made, and the specimens were submitted to TMA. New replicas were made from the aged specimens for marginal adaptation analysis by scanning electron microscopy. Data were submitted to Kruskal-Wallis and Wilcoxon tests (α=0.05). Before TMA, when enamel was etched before the application of S3, no gap formation was observed; however, there were gaps at the interface for the other tested conditions, with a statistical difference (p≤0.05). After TMA, the selective enamel etching previous to the S3 application, regardless of the LCU, promoted higher marginal adaptation compared to the other tested groups (p≤0.05). Prior to TMA, higher marginal integrity was observed, in comparison with specimens after TMA (p≤0.05). With regard to Clearfil SE and Clearfil Tri-S cured with FL, no differences of gap formation were found between before and after aging (5.3 ± 3.8 and 7.4 ± 7.5, respectively), especially when the Clearfil Tri-S was used in the conventional protocol. When cured with RD or UL and not etched, Clearfil Tri-S presented the higher gap formation. In conclusion, additional enamel etching promoted better marginal integrity for Clearfil Tri-S, showing it to be an efficient technique for Class I composite restorations. The two-step self-etch adhesive was not influenced by selective enamel etching or by the LED-curing unit.