On the basis of our experience, MRI is an excellent, safe and, reliable modality to confirm maintenance of adequate femoral head position and to evaluate soft tissue interposition. We agree that MRI is the gold standard to early depict dislocation after closed reduction of DDH.
Human papillomavirus (HPV)-associated tumors still represent an urgent problem of public health in spite of the efficacy of the prophylactic HPV vaccines. Specific antibodies in single-chain format expressed as intracellular antibodies (intrabodies) are valid tools to counteract the activity of target proteins. We previously showed that the M2SD intrabody, specific for the E7 oncoprotein of HPV16 and expressed in the endoplasmic reticulum of the HPV16-positive SiHa cells, was able to inhibit cell proliferation. Here, we showed by confocal microscopy that M2SD and E7 colocalize in the endoplasmic reticulum of SiHa cells, suggesting that the E7 delocalization mediated by M2SD could account for the anti-proliferative activity of the intrabody. We then tested the M2SD antitumor activity in two mouse models for HPV tumors based respectively on TC-1 and C3 cells. The M2SD intrabody was delivered by retroviral vector to tumor cells before cell injection into C57BL/6 mice. In both models, a marked delay of tumor onset with respect to the controls was observed in all the mice injected with the M2SD-expressing tumor cells and, importantly, a significant percentage of mice remained tumor-free permanently. This is the first in vivo demonstration of the antitumor activity of an intrabody directed towards an HPV oncoprotein. We consider that these results could contribute to the development of new therapeutic molecules based on antibodies in single-chain format, to be employed against the HPV-associated lesions even in combination with other drugs.Human papillomaviruses (HPVs) belonging to 15 genotypes defined as "high risk," are the recognized cause of an increasing number of malignancies among which cervical cancer (CC) is the most represented in women worldwide.1,2 Despite the high protective efficacy of the HPV vaccine, expected to reduce the number of HPV-associated cancers in the coming decades, non-invasive therapies are urgently needed for avoiding overtreatment of pre-tumor lesions and preventing or treating metastatic lesions in the case of established tumors, particularly for the treatment of immunosuppressed people. 3The E6 and E7 oncoproteins of the high risk genotypes are tumor-specific antigens expressed in tumors and precursor lesions; they contribute to viral immunoevasion and act in concert to promote tumor development through the interaction with multiple cellular proteins. The E7 mainly affects factors involved in proliferation and cell cycle regulation, such as the retinoblastoma (pRb) and the whole pocket proteins family, the p21 and p27 cyclin-dependent kinase inhibitors, and the cyclins A and E, whereas the E6 binds to the p53 tumor suppressor through the E6-AP and to Bak proteins to ensure hampering of cell apoptosis.4,5 Therefore, E6 and E7 represent ideal targets for antitumor therapeutic interventions. Several approaches were and are currently explored to counteract the oncoproteins at gene or protein level. 6 In the last decades, emerged the possibility of designing drugs based on antibodies again...
BackgroundThe growing cost of health care and lack of specialised staff have set e-Health high on the European political agenda. In a prospective study we evaluated the effect of providing images for remote consultation through an iPad on the number of in-hospital orthopaedic consultations for children with bone fractures.MethodsChildren from 0 to 18 years diagnosed with a bone fracture by the radiologist during the hours when an orthopaedic service is provided only on-call were eligible for enrollment. Cases were enrolled prospectively during September and October 2013. A standard approach (verbal information only, no X-Ray provided remotely) was compared to an experimental approach (standard approach plus the provision of X-ray for remote consultation through an iPad). The primary outcome was the number of orthopaedic in-hospital consultations that occurred. Other outcomes included: immediate activation of other services; time needed for decision-making; technical difficulties; quality of images and diagnostic confidence (on a likert scale of 1 to 10).ResultsForty-two children were enrolled in the study. Number of in-hospital consultancies dropped from 32/42 (76.1%) when no X-ray was provided to 16/42 (38%) when the X-rays was provided (p < 0.001). With remote X-ray consultation in 14/42 (33.3%) cases services such as surgery and plaster room could be immediately activated, compared to no service activated without teleradiology (p < 0.001). Average time for decision making was 23.4 ± 21.8 minutes with remote X-ray consultation, compared to 56.2 ± 16.1 when the X-ray was not provided (p < 0.001). The comparison between images on the iPad and on the standard system for X- Ray visualisation resulted in a non statistically significant difference in the quality of images (average score 9.89 ± 0.37 vs 9.91 ± 0.30; p =0.79), and in non statistically significant difference in diagnostic confidence (average score 9.91 ± 0.32 vs 9.92 ± 0.31; p = 0.88).ConclusionsRemote X-ray consultation through Aycan OsiriX PRO and iPad should be considered as a means for reducing the need of in-hospital orthopaedic consultation during on-call times, and potentially decrease the cost of care for the health system. In the future, alternative systems less expensive than Aycan OsiriX PRO should be further developed and tested.
Congenital clubfoot is a common pediatric malformation that affects approximately 0.1% of all births. 80% of the cases appear isolated, while 20% can be secondary or associated with complex syndromes. To date, two genes that appear to play an important role are PTIX1 and TBX4, but their actual impact is still unclear. Our study aimed to evaluate the prevalence of pathogenic variants in PITX1 and TBX4 in Italian patients with idiopathic clubfoot. PITX1 and TBX4 genes were analyzed by sequence and SNP array in 162 patients. We detected only four nucleotide variants in TBX4, predicted to be benign or likely benign. CNV analysis did not reveal duplications or deletions involving both genes and intragenic structural variants. Our data proved that the idiopathic form of congenital clubfoot was rarely associated with mutations and CNVs on PITX1 and TBX4. Although in some patients, the disease was caused by mutations in both genes; they were responsible for only a tiny minority of cases, at least in the Italian population. It was not excluded that other genes belonging to the same TBX4-PITX1 axis were involved, even if genetic complexity at the origin of clubfoot required the involvement of other factors.
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