Long-term outcome of primary non-surgical root canal treatment

Aim: The aim of this study is to examine the survival distributions of primary root canal treatment using interval-censored data and to assess the factors affecting the outcome of primary root canal treatment, in terms of periapical healing and tooth survival. Materials and methods: About one tenth of primary root canal treatment performed between January 1981 and December 1994 in a dental teaching hospital were systematically sampled for inclusion in this study. Information about the patients' personal particulars, medical history, pre-operative status, treatment details, and previous review status of the treated teeth, were obtained from dental records. Patients were recalled for examination clinically and radiographically. Treatment outcomes were categorized according to the status for periapical healing and tooth survival. The event time was interval-censored and subjected to survival analysis using the Weibull accelerated failure time model. Results: A total of 889 teeth were suitable for analysis. Survival curves of both outcome measures (periapical healing and tooth survival) declined in a non-linear fashion with time. Median survival of the treated teeth was 119 months (periapical healing) and 252 months (tooth survival). Age, tooth type, pre-operative periapical status, occlusion, type of final restoration, and condition of the tooth/restoration margin were significant factors affecting both periapical healing and tooth survival. Apical extent and homogeneity of root canal fillings had a significant impact towards periapical healing (p < 0.05), but not tooth survival. Conclusion: The longevity of treated teeth based on tooth survival was considerably greater than that of periapical healing. Both outcome measures were affected by a number of socio-demographic, pre-, intra-, and post-operative factors. Clinical relevance: Root canal-treated teeth may continue to function for a considerable period of time even though there may be radiographic periapical lesion present. Decision for extraction may be due to reasons other than a failure of the periapical tissues to heal. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 28 May 201

Pdxdc1 modulates prepulse inhibition of acoustic startle in the mouse.

Current antipsychotic medications used to treat schizophrenia all target the dopamine D2 receptor. Although these drugs have serious side effects and limited efficacy, no novel molecular targets for schizophrenia treatment have been successfully translated into new medications. To identify novel potential treatment targets for schizophrenia, we searched for previously unknown molecular modulators of acoustic prepulse inhibition (PPI), a schizophrenia endophenotype, in the mouse. We examined six inbred mouse strains that have a range of PPI, and used microarrays to determine which mRNA levels correlated with PPI across these mouse strains. We examined several brain regions involved in PPI and schizophrenia: hippocampus, striatum, and brainstem, found a number of transcripts that showed good correlation with PPI level, and confirmed this with real-time quantitative PCR. We then selected one candidate gene for further study, Pdxdc1 (pyridoxal-dependent decarboxylase domain containing 1), because it is a putative enzyme that could metabolize catecholamine neurotransmitters, and thus might be a feasible target for new medications. We determined that Pdxdc1 mRNA and protein are both strongly expressed in the hippocampus and levels of Pdxdc1 are inversely correlated with PPI across the six mouse strains. Using shRNA packaged in a lentiviral vector, we suppressed Pdxdc1 protein levels in the hippocampus and increased PPI by 70%. Our results suggest that Pdxdc1 may regulate PPI and could be a good target for further investigation as a potential treatment for schizophrenia

Non-genetic expression of adolescent idiopathic scoliosis: a case report and review of the literature

Treating children with idiopathic scoliosis can amaze someone at the many different ways in which the deformity can present. Most authors state that genetics stipulates the course of adolescent idiopathic scoliosis. This is mainly based on the high concordance in monozygotic twins. However, there is indication that environmental factors have influences on adolescent idiopathic scoliosis. This is the first report in which a monozygotic twin pair is described concordant for idiopathic scoliosis but with different apical levels, magnitudes and age at detection of scoliosis which stresses the importance of environmental factors

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours.

G-quadruplex DNAs form four-stranded helical structures and are proposed to play key roles in different cellular processes. Targeting G-quadruplex DNAs for cancer treatment is a very promising prospect. Here, we show that CX-5461 is a G-quadruplex stabilizer, with specific toxicity against BRCA deficiencies in cancer cells and polyclonal patient-derived xenograft models, including tumours resistant to PARP inhibition. Exposure to CX-5461, and its related drug CX-3543, blocks replication forks and induces ssDNA gaps or breaks. The BRCA and NHEJ pathways are required for the repair of CX-5461 and CX-3543-induced DNA damage and failure to do so leads to lethality. These data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. CX-5461 is now in advanced phase I clinical trial for patients with BRCA1/2 deficient tumours (Canadian trial, NCT02719977, opened May 2016).This work was supported by the Canadian Breast Cancer Foundation BC/Yukon, BC Cancer Foundation, Stand Up to Cancer Canada (SU2C-AACR-DT-18-15), TFRI Grant 1021, CCSRI Grant 701584, CIHR Grant MOP-126119, Canada Foundation for Innovation and Cancer Research UK. Grant Brown lab is supported by CCSRI Impact Grant 702310 (to G.W.B.) and Ontario Government Scholarship (to B.H.). S.A. is supported by a Canada Research Chair in Molecular Oncology. The Balasubramanian lab is supported by a programme grant (C14303/A17197) and core funding (C14303/A17197) from Cancer Research UK

Choroidal evaluation using enhanced depth imaging spectral-domain optical coherence tomography in Vogt-Koyanagi-Harada disease

BACKGROUND: Current imaging modalities used in the evaluation of Vogt-Koyanagi-Harada (VKH) disease include ultrasound, fluorescein angiogram, indocyanine green angiography, and optical coherence tomography (OCT). However, they all fail to give detailed information on the ultrastructural changes of the choroid. A recent technique using OCT termed "enhanced depth imaging" produces high-resolution cross-sectional images of the whole thickness of the choroid. The purpose of the study was to describe a novel imaging finding in the choroid in cases of VKH uveitis and to assess for interobserver agreement of this new physical sign. METHODS: This is an age-matched, sex-matched, and spherical equivalent-matched, case-control, cross-sectional study. Six VKH patients in acute and convalescent stages underwent choroidal imaging using enhanced depth imaging spectral-domain OCT imaging. A horizontal enhanced depth imaging spectral-domain OCT scan across the fovea was selected for each eye and was compared with a scan from an age-matched, sex-matched, and spherical equivalent-matched control subject. A loss of focal hyperreflectivity, represented by a decrease in the number of hyperreflective dots in the inner choroid, was observed. This finding was assessed for interobserver agreement using five masked observers. Mean observed agreement and multirater kappa statistics (κ) were calculated. The average choroidal thickness was also calculated and compared among acute-phase VKH patients, convalescent-phase VKH patients, and control subjects. RESULTS: There was a significant loss of focal hyperreflectivity in the inner choroid of VKH patients compared with control subjects in both acute and convalescent stages. Analysis revealed substantial interobserver agreement on this finding. The mean observed agreement was 95%, and the overall kappa coefficient (κ) was 0.80 (P < 0.01). The choroid of acute-phase VKH patients was thicker than that of convalescent-phase patients by 151 μm (P = 0.043) and control subjects by 137 μm (P = 0.001). There was no statistically significant difference in thickness between convalescent eyes and controls. CONCLUSION: Enhanced depth imaging spectral-domain OCT highlights a loss of focal hyperreflectivity in the inner choroid of eyes with VKH, a feature that is consistently observed by independent masked observers. The presence of this feature in both acute and convalescent phases could represent permanent structural change to small choroidal vessels caused by VKH uveitis. © The Ophthalmic Communications Society, Inc.link_to_subscribed_fulltex

Choroidal neovascularaization secondary to Klebsiella pneumoniae endogenous abscess and endophthalmitis

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Volunteer training programme in the community end-of-life care: a competence-based structured training program

Organised by the Jockey Club End-of-Life Community Care Project (JCECC), Faculty of Social Sciences, the University of Hong Kon

Pdxdc1 modulates prepulse inhibition of acoustic startle in the mouse.

Current antipsychotic medications used to treat schizophrenia all target the dopamine D2 receptor. Although these drugs have serious side effects and limited efficacy, no novel molecular targets for schizophrenia treatment have been successfully translated into new medications. To identify novel potential treatment targets for schizophrenia, we searched for previously unknown molecular modulators of acoustic prepulse inhibition (PPI), a schizophrenia endophenotype, in the mouse. We examined six inbred mouse strains that have a range of PPI, and used microarrays to determine which mRNA levels correlated with PPI across these mouse strains. We examined several brain regions involved in PPI and schizophrenia: hippocampus, striatum, and brainstem, found a number of transcripts that showed good correlation with PPI level, and confirmed this with real-time quantitative PCR. We then selected one candidate gene for further study, Pdxdc1 (pyridoxal-dependent decarboxylase domain containing 1), because it is a putative enzyme that could metabolize catecholamine neurotransmitters, and thus might be a feasible target for new medications. We determined that Pdxdc1 mRNA and protein are both strongly expressed in the hippocampus and levels of Pdxdc1 are inversely correlated with PPI across the six mouse strains. Using shRNA packaged in a lentiviral vector, we suppressed Pdxdc1 protein levels in the hippocampus and increased PPI by 70%. Our results suggest that Pdxdc1 may regulate PPI and could be a good target for further investigation as a potential treatment for schizophrenia