Observations on an in-vivo failure of a titanium dental implant/abutment screw system: a case report

Titanium and its alloys are widely used in prosthetic dentistry, due to their biocompatibility, excellent mechanical and anti-corrosion behavior. However, delayed fracture of dental prosthetics is frequently encountered. Mechanisms leading to fracture are not generic but are strongly related to the particular environmental (quality of biological fluids) and mechanical loading conditions (mastication habits, presence of prosthetic metallic/ceramic components) in the patients' oral cavity. In this study, a commercially pure titanium implant-screw system has failed after 15 years of operation in the oral cavity of an old female. The system was retrieved in three pieces: the upper part of the implant, part of the abutment screw, and the apical part of the implant to which a part of the screw was embedded. This is considered as a rare case, where the whole dental assembly was retrieved after fracture allowing the extensive fractographic analysis of the conjugate pieces and the establishment of a thorough in-vivo failure scenario. Scanning electron microscopy observations performed on all three retrieved parts indicated a synergistic effect of distinct mechanisms, which led to total failure under extrinsic common fatigue loading. The principal mechanism was the propagation of a main crack, which was previously initiated in the body of the implant and affected by a wedging mechanism due to Ca/P aggregates developed within the crack. Because of the strong fixation between the implant and the abutment screw, this main crack was transferred to the latter causing eventually total failure of the assembly.     

A combined computational-experimental approach predicts human microRNA targets

A new paradigm of gene expression regulation has emerged recently with the discovery of microRNAs (miRNAs). Most, if not all, miRNAs are thought to control gene expression, mostly by base pairing with miRNA-recognition elements (MREs) found in their messenger RNA (mRNA) targets. Although a large number of human miRNAs have been reported, many of their mRNA targets remain unknown. Here we used a combined bioinformatics and experimental approach to identify important rules governing miRNA-MRE recognition that allow prediction of human miRNA targets. We describe a computational program, "DIANA-microT", that identifies mRNA targets for animal miRNAs and predicts mRNA targets, bearing single MREs, for human and mouse miRNAs.     

Hepatitis C virus knowledge improves hepatitis C virus screening practices among primary care physicians

AIM To understand the role of knowledge as a promoter of hepatitis C virus(HCV) screening among primary care physicians(PCP).METHODS A 45-item online questionnaire assessing knowledge of HCV natural history, risk factors, and treatment was distributed to 163 PCP. Logistic regression, adjusted for survey responses, assessed associations between PCP knowledge of HCV natural history and treatment and birth cohort(i.e., birth between 1945 and 1965) screening. Response stratification and weighting were used to account for nonresponse and to permit extension of responses to the entire survey population. Associations between various predictors including demographic characteristics, level of training, and HCV treatment experience and HCV knowledge were assessed.RESULTS Ninety-one individuals(55.8%) responded. Abnormal liver enzymes(49.4%), assessment of HCV-related risk factors(30.6%), and birth cohort membership(20%) were the leading HCV screening indications. Most PCP(64.7%) felt that the combination of risk-factor and birth cohort screening utilizing a self-administered survey while awaiting the physician(55.3%) were the most efficient screening practices. Implementation of birth cohort screening was associated with awareness of the recommendations(P-value = 0.01), knowledge of HCV natural history(P-value 0.01), and prior management of HCV patients(P-value 0.01). PCP with knowledge of HCV treatment was also knowledgeable about HCV natural history(P-value 0.01). Similarly, awareness of age-based screening recommendations was associated with HCV treatment knowledge(P-value = 0.03).CONCLUSION Comprehensive knowledge of HCV is critical to motivate HCV screening. PCP-targeted educational interventions are required to expand the HCV workforce and linkageto-care opportunities as we seek global HCV eradication.     

Long-Term Results of Postoperative Hypofractionated Accelerated Breast and Lymph Node Radiotherapy (HypoAR) with Hypofractionated Boost

We report long-term results (median follow-up 12 years) of hypofractionated accelerated radiotherapy (HypoAR) in patients treated with breast-conserving surgery. In total, 367 women were treated with HypoAR. Axillary and supraclavicular area (ASA) were treated in patients with involved nodes. In total, 290 patients (scheme A) received 3.5 Gy/day ×10 fractions (breast/ASA) followed by two 4 Gy fractions with electrons to the affected breast quadrant within 16 days. In total, 77 patients (Scheme B) received 2.7 Gy/day for 16 consecutive fractions (breast/ASA) within 22 days, while concurrently, the affected breast quadrant received an electron booster dose of 0.8 Gy for the first 13 fractions. Amifostine was offered to 252/367 patients. Early radiation toxicity was minimal. Regarding late toxicities, symptomatic breast edema was noted in 2.2%, asymptomatic breast fibrosis in 1.9%, and arm lymphedema in 3.7% of patients. Amifostine reduced early radiation dermatitis (p = 0.001). In total, 2.2% of patients developed contralateral breast and 1.6% other carcinomas. Locoregional recurrence (LR) occurred in 3.1% of patients (0% for in situ carcinomas). Positive margins after surgery, extracapsular node invasion, and HER2-enriched/triple-negative tumors were linked with significantly worse LR-free survival. The involvement of more than three nodes and luminal type other than A were independent prognostic variables of metastasis and death events. HypoAR delivering a biological dose of 50–52 Gy to the breast/ASA is a safe and effective therapy for patients treated with conservative surgery. The risk of carcinogenesis is low. Positive surgical margins, extracapsular node invasion, and HER2-enriched/triple-negative phenotypes appear as a cluster of features linked with a higher risk for locoregional relapse.     

Cerebrospinal fluid of patients administered moxifloxacin modulates the secretion of cytokines from human monocytes

To evaluate the ex vivo immunomodulatory properties of moxifloxacin, we applied serum and cerebrospinal fluid (CSF) samples from 50 patients who received a single oral dose of 400 mg. Patients were divided into 5 groups according to time lapsing between sampling and drug intake: group I, 0.5 to 1 h; group II, 1 to 2 h; group III, 2 to 4 h; group IV, 4 to 6 h; and group V, 6 to 8 h. Samples were added to cultures of U937 monocytes stimulated by 10 ng/mL of lipopolysaccharide (LPS) and 1 x 10(5) colony-forming unit (CFU) of 1 heat-killed penicillin-resistant isolate of Streptococcus pneumoniae. Concentrations of cytokines were estimated in supernatants. Concentrations of interleukin (IL)-1beta, IL-10, and IL-12 released after stimulation by LPS were significantly decreased by CSF of groups I, IV, and V. After stimulation by the heat-killed isolate, concentrations of tumor necrosis factor alpha (TNF-alpha), IL-1beta, IL-6, and IL-10 were increased in the presence of CSF of group III; those of IL-12p70 were decreased by CSF of groups I and II. Concentrations of IL-1beta, IL-6, and IL-8 drawn after stimulation by LPS were significantly decreased upon addition of serum from all groups. After stimulation by the heat-killed isolate, concentrations of TNF-alpha were decreased by serum drawn from all patients; IL-1beta was increased after addition of serum of groups I, II, and V. It is concluded that CSF and serum of patients administered moxifloxacin may effectively modulate the production of pro- and anti-inflammatory cytokines by human monocytes. These results render new perspectives for the therapy for meningitis.     

A pilot study on plasma levels of micro-RNAs involved in angiogenesis and vascular maturation in patients with breast cancer

Micro-RNAs (miRNAs) have a complex role in carcinogenesis and tumour progression. Several miRNAs, such as miR-221, miR-27b and miR-132, have been implicated in the regulation of VEGF tumour angiogenic activity. In this pilot study, we assessed angiogenesis and DLL4+ vascular maturation index (VMI) in breast cancer tissues, in parallel with the plasma levels of the above-mentioned miRNAs. Significantly higher than control samples pre-operative levels were recorded in 10/11, 7/11 and 9/11 cases for the miR-221, miR-27b and miR-132, respectively. Seven days after surgery, a significant reduction of these miRNAs was noted in 6/11, 3/11 and 2/11 cases, respectively. High pre-operative levels of miR-27b were linked with node metastasis (p = 0.04). High pre-operative levels of miR-132 were linked with small tumours (p = 0.03) and her2 overexpression (p = 0.003). The DLL4+ VMI ranged from 26 to 69% (median 45%). Patients with poor DLL4+ VMI had significantly high pre-operative and post-operative levels of miR-221 (p = 0.01 and 0.02, respectively) and high post-operative levels of miR-132 (p = 0.02). It is concluded that angiogenesis-related miRs as detected in the plasma of patients may prove of a useful tool in the identification of patients with poor vascular maturation and high risk to develop metastasis. Whether such miRs may identify patients who would benefit from vascular normalization policies is a hypothesis that emerges from the current study.     

A high-resolution RNA expression atlas of retinitis pigmentosa genes in human and mouse retinas

PURPOSE: Retinitis pigmentosa (RP) is one of the leading causes of visual handicap in the world population and is characterized by high genetic heterogeneity. The study of the disease mechanisms and the development of efficient therapeutic approaches have mostly relied on the availability of animal models for this condition, so far. Nevertheless, little information is available about the RNA expression profiles of RP genes in the human retina. An expression atlas of 34 known RP genes in human and murine retinas was generated to overcome this lack of information. METHODS: Appropriate templates were retrieved for 34 RP genes that were used to perform RNA in situ hybridization studies on human and murine adult eyes. RESULTS: Most of the genes displayed similar patterns between human and mouse retina. Different expression patterns were observed for the CNGB1, USH2A, and FSCN2 genes, compared with those in previously reported profiles. In addition, different expression profiles were detected for the RPGR, CA4, PAP1, RGR, and RLBP1 genes in human and mouse retinas. CONCLUSIONS: The first gene expression atlas has been generated of RP genes in human and murine retinas. Differences observed in the expression patterns of some genes in humans and mice, will open new perspectives on the function of these genes and their putative roles in disease pathogenesis.     

A longitudinal study of cognitive function in multiple sclerosis: is decline inevitable?

Journal of Neurology - Numerous cross-sectional studies report cognitive impairment in multiple sclerosis (MS), but longitudinal studies with sufficiently long-term follow-up are scarce. We aimed...