Homozygous Recessive Versican Missense Variation Is Associated With Early Teeth Loss in a Pakistani Family.

Only a few genes involved in teeth development and morphology are known to be responsible for tooth abnormalities in Mendelian-inherited diseases. We studied an inbred family of Pakistani origin in which two first-cousin born brothers are affected by early tooth loss with peculiar teeth abnormalities characterized by the absence of cementum formation. Whole exome sequencing revealed a H2665L homozygous sequence variant in the VCAN gene. Dominant splicing mutations in VCAN are known to cause Wagner syndrome or vitreoretinopathy. We explored teeth morphology in these two patients, while versican expression was assessed by western blot analysis. Early signs of vitreoretinopathy were found in the elder brother while the parents were completely negative. Our findings suggest that the homozygous recessive H2665L missense sequence variant impairs the normal morphology of the teeth roots via loss of cementum synthesis, and is also associated with early onset, recessive, Wagner syndrome, thus expanding both the phenotype mutation scenario and the inheritance mode of VCAN mutations.

[Laparoscopic incisional hernia repair: our experience and review of the literature]. / La riparazione laparoscopica del laparocele. Revisione della letteratura e nostra esperienza.

Incisional hernia after laparotomy closure continues to be an important postoperative complication. Historically, the best results have been obtained with the open Rives-Stoppa technique. This approach is done by fixing a prosthetic mesh behind the posterior fascia of the rectus muscle. The laparoscopic approach allows similar mesh placement with minimal dissection. In this study, we review the scientific literature and report our experience, describing the clinical outcome of patients who have undergone laparoscopic repair of ventral hernias. After describing the standard technique of laparoscopic insertion of a prosthesis, we reviewed the records of all our patients who underwent such a procedure from March 2004 to January 2006. A laparoscopic approach was attempted in all patients. The patients' demographic characteristics, operative details and outcomes were recorded. Of 55 patients scheduled to undergo laparoscopic incisional herniorrhaphy, conversion to an open procedure was necessary in 2/55 (3.6%). All the remaining 53 patients (31 men and 22 women; mean age 51.8 years) underwent laparoscopic repair of ventral hernias. The mean fascial defect size was 98.3 cm (range: 5-200 cm). In 52/53 patients (98%) a dual mesh was used. 40% of patients (22/53) had multiple wall defects. The mean operative time was 90 minutes (range: 32-190 minutes). The average hospital stay was 2.6 days (range: 1-16 days). 50/53 patients (94.3%) tolerated an oral diet 24 hours after the operation. 49/53 (92.4%) returned to normal working activity within two weeks. The percentage of complications amounted to 13% (7/55), with 5.6% (5/53) minor and 3.7% (2/55) major complications. In one patient it was necessary to remove the mesh 6 months after surgery because of pain. The recurrence rate of 5.6% confirms the permanence of the repair. The follow-up was 12 months for 44/53 patients and 6 months for 9/53 patients. The procedure for incisional hernia repair used in our study may be performed safely with low complication and recurrence rates and should be considered for the majority of incisional hernia repairs requiring a mesh prosthesis.

Nanoparticle-based strategies for cancer immunotherapy and immunodiagnostics.

Although recent successes in clinical trials are strengthening research focused on cancer immunology, the poor immunogenicity and off-target side effects of immunotherapeutics remain major challenges in translating these promising approaches to clinically feasible therapies in the treatment of a large range of tumors. Nanotechnology offers target-based approaches, which have shown significant improvements in the rapidly advancing field of cancer immunotherapy. Here, we first discuss the chemical and physical features of nanoparticulate systems that can be tuned to address the anticancer immune response, and then review recent, key examples of the exploited strategies, ranging from nanovaccines to NPs revising the tumor immunosuppressive microenvironment, up to immunotherapeutic multimodal NPs. Finally, the paper concludes by identifying the promising and outstanding challenges the field of emerging nanotechnologies is facing for cancer immunotherapy.

Combined microcomputed tomography, biomechanical and histomorphometric analysis of the peri-implant bone: a pilot study in minipig model.

OBJECTIVES: To present a practical approach that combines biomechanical tests, microcomputed tomography (µCT) and histomorphometry, providing quantitative results on bone structure and mechanical properties in a minipig model, in order to investigate the specific response to an innovative dental biomaterial. METHODS: Titanium implants with innovative three-dimensional scaffolds were inserted in the tibias of 4 minipigs. Primary stability and osseointegration were investigated by means of insertion torque (IT) values, resonance frequency analysis (RFA), bone-to-implant contact (BIC), bone mineral density (BMD) and stereological measures of trabecular bone. RESULTS: A significant positive correlation was found between IT and RFA (r=0.980, p=0.0001). BMD at the implant sites was 18% less than the reference values (p=0.0156). Peri-implant Tb.Th was 50% higher, while Tb.N was 50% lower than the reference zone (p<0.003) and they were negatively correlated (r=-0.897, p=0.006). SIGNIFICANCE: µCT increases evaluation throughput and offers the possibility for qualitative three-dimensional recording of the bone-implant system as well as for non-destructive evaluation of bone architecture and mineral density, in combination with conventional analysis methods. The proposed multimodal approach allows to improve accuracy and reproducibility for peri-implant bone measurements and could support future investigations.