Efficacy of direct pulp capping for management of cariously exposed pulps in permanent teeth: a systematic review and meta-analysis.

BACKGROUND: The outcome of vital pulp treatment after carious pulp exposure is multifactorial and related to the procedure, biomaterial and pre-operative pulpal diagnosis. OBJECTIVES: To conduct a systematic review and meta-analysis determining the outcome of direct pulp capping (DPC) in mature permanent teeth with a cariously exposed pulp and a clinical diagnosis of reversible pulpitis, and ascertain whether the capping material influences the outcome. METHODS: Sources: MEDLINE Ovid-SP, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, Embase and Web of Science until April 2020. Inclusion: Prospective, retrospective cohort studies and randomized trials investigating DPC outcome or comparing different capping materials after carious pulp exposure. Exclusion: Primary teeth, mechanical, traumatic or not specified pulp exposure, teeth with irreversible pulpitis or no pulpal diagnosis. Risk of bias assessed using Cochrane and modified Downs and Black quality assessment checklist. Meta-analysis on combined clinical/radiographic outcome was performed using a random effect model. Success was defined as absence of signs and symptoms of irreversible pulpitis, apical periodontitis or loss of pulp vitality. RESULTS: Quality assessment highlighted four non-randomized studies to be of fair and five of poor quality. Four randomized trials had a high risk of bias. The pooled success rate differed based on material and follow-up. Calcium hydroxide success rate was 74% at 6-months, 65% at 1-year, 59% at 2-3 years and 56% at 4-5 years. Mineral trioxide aggregate (MTA) success was 91%, 86%, 84% and 81% at the same time points. Biodentine success was 96% at 6-months, 86% at 1 year and 86% at 2-3 years. The meta-analysis revealed MTA had better success than calcium hydroxide at 1-year (OR 2.66, 95% CI; 1.46- 4.84, P = 0.001) and 2- to 3-year follow-up (OR 2.21, 95% CI; 1.42-3.44, P = 0.0004). There was no difference between MTA and Biodentine. DISCUSSION: These results were based on poor methodological quality studies. The effect size for of MTA vs Ca(OH)2, although modest, was consistent with narrow CI. CONCLUSIONS: Low-quality evidence suggests a high success rate for direct pulp capping in teeth with cariously exposed pulps with better long-term outcomes for MTA and Biodentine compared with calcium hydroxide.

Automated differentiation of pre-diagnosis Huntington's disease from healthy control individuals based on quadratic discriminant analysis of the basal ganglia: the IMAGE-HD study.

We investigated two measures of neural integrity, T1-weighted volumetric measures and diffusion tensor imaging (DTI), and explored their combined potential to differentiate pre-diagnosis Huntington's disease (pre-HD) individuals from healthy controls. We applied quadratic discriminant analysis (QDA) to discriminate pre-HD individuals from controls and we utilised feature selection and dimension reduction to increase the robustness of the discrimination method. Thirty six symptomatic HD (symp-HD), 35 pre-HD, and 36 control individuals participated as part of the IMAGE-HD study and underwent T1-weighted MRI, and DTI using a Siemens 3 Tesla scanner. Volume and DTI measures [mean diffusivity (MD) and fractional anisotropy (FA)] were calculated for each group within five regions of interest (ROI; caudate, putamen, pallidum, accumbens and thalamus). QDA was then performed in a stepwise manner to differentiate pre-HD individuals from controls, based initially on unimodal analysis of motor or neurocognitive measures, or on volume, MD or FA measures from within the caudate, pallidum and putamen. We then tested for potential improvements to this model, by examining multi-modal MRI classifications (volume, FA and MD), and also included motor and neurocognitive measures, and additional brain regions (i.e., accumbens and thalamus). Volume, MD and FA differed across the three groups, with pre-HD characterised by significant volumetric reductions and increased FA within caudate, putamen and pallidum, relative to controls. The QDA results demonstrated that the differentiation of pre-HD from controls was highly accurate when both volumetric and diffusion data sets from basal ganglia (BG) regions were used. The highest discriminative accuracy however was achieved in a multi-modality approach and when including all available measures: motor and neurocognitive scores and multi-modal MRI measures from the BG, accumbens and thalamus. Our QDA findings provide evidence that combined multi-modal imaging measures can accurately classify individuals up to 15 years prior to onset when therapeutic intervention is likely to have maximal effects in slowing the trajectory of disease development.

Lifestyle factors associated with cardiovascular risk among healthcare workers from the tertiary hospitals in Sarawak.

INTRODUCTION: A cross-sectional study is used to evaluate the lifestyle factors associated with cardiovascular disease (CVD) risk among healthcare workers in tertiary hospitals in Sarawak, Malaysia. METHODS: A questionnaire-based survey using the Simple Lifestyle Indicator Questionnaire (SLIQ) was administered to, and anthropometric measurements were collected from, 494 healthcare workers. RESULTS: The mean age of the subjects was 32.4±8.4, with a range of 19 to 59 years. The subjects were from the allied health (45.5%), management and professional (25.1%) and executive (29.4%) fields. Overall, 47.4% of the subjects were of normal weight, 30.2% were overweight, 17.2% were obese and 5.2% were underweight. The mean number of working hours per week for the subjects was 47.6±14.0 with the highest working hours found among the management and professional group, followed by the executive and allied health groups. Overall, 39.7% of the healthcare workers worked office hours, 36.6% worked within the shift system, 20.9% worked office hours and were on-call and the remaining 2.8% worked a mixture of office hours and shifts. Based on the SLIQ score, 58.1% were classified as at intermediate risk for CVD, 38.5% were in the healthy category and 3.4% were in the unhealthy category. Factors associated with a healthier lifestyle were being female (Odds Ratio [OR]= 12.1; CI=3.2-46.4), professional (mean score= 6.70), in the allied health group (mean score=7.33) and in the normal BMI group (OR= 9.3, CI= 1.8-47.0). CONCLUSION: In our study, healthcare workers had an intermediate risk of developing CVD in the future. Thus, there is a need to intervene in the lifestyle factors contributing to CVD.

Bioactive titanium implant surfaces with bacterial inhibition and osteoblast function enhancement properties.

Infection in orthopedic implant surgery is a serious complication and a major cause of implant failure. Upon implant insertion, a contest between microbial colonization and tissue integration of the implant surface ensues. This race for the surface determines the probability of tissue integration or infection, and the surface properties of the substrate have an important role to play in determining the outcome. A number of strategies have been developed for the modification of implant surfaces to promote bone cell (osteoblast) functions and inhibit bacterial adhesion and growth. In this article, a review is given of these surface modification strategies, in particular those which can achieve the dual aim of bacterial inhibition and simultaneous enhancement of osteoblast functions.Surfaces of these types can be expected to have excellent potential for orthopedic applications.

Functional connectivity of the prefrontal cortex in Huntington's disease.

BACKGROUND: Huntington's disease is a progressive neurodegenerative disorder that results in deterioration and atrophy of various brain regions. AIM: To assess the functional connectivity between prefrontal brain regions in patients with Huntington's disease, compared with normal controls, using functional magnetic resonance imaging. PATIENTS AND METHODS: 20 patients with Huntington's disease and 17 matched controls performed a Simon task that is known to activate lateral prefrontal and anterior cingulate cortical regions. The functional connectivity was hypothesised to be impaired in patients with Huntington's disease between prefrontal regions of interest, selected from both hemispheres, in the anterior cingulate and dorsal lateral prefrontal cortex. RESULTS: Controls showed a dynamic increase in interhemispheric functional connectivity during task performance, compared with the baseline state; patients with Huntington's disease, however, showed no such increase in prefrontal connectivity. Overall, patients with Huntington's disease showed significantly impaired functional connectivity between anterior cingulate and lateral prefrontal regions in both hemispheres compared with controls. Furthermore, poor task performance was predicted by reduced connectivity in patients with Huntington's disease between the left anterior cingulate and prefrontal regions. CONCLUSIONS: This finding represents a loss of synchrony in activity between prefrontal regions in patients with Huntington's disease when engaged in the task, which predicted poor task performance. Results show that functional interactions between critical prefrontal regions, necessary for cognitive performance, are compromised in Huntington's disease. It is speculated whether significantly greater levels of activation in patients with Huntington's disease (compared with controls) observed in several brain regions partially compensate for the otherwise compromised interactions between cortical regions.

Bdf1, a yeast chromosomal protein required for sporulation.

The BDF1 gene of Saccharomyces cerevisiae is required for sporulation. Under starvation conditions, most cells from the bdf1 null mutant fail to undergo one or both meiotic divisions, and there is an absolute defect in spore formation. The Bdf1 protein localizes to the nucleus throughout all stages of the mitotic and meiotic cell cycles. Analysis of spread meiotic nuclei reveals that the Bdf1 protein is localized fairly uniformly along chromosomes, except that it is excluded specifically from the nucleolus. A bdf1 null mutant displays a reduced rate of vegetative growth and sensitivity to a DNA-damaging agent. The BDF1 gene encodes a 77-kDa protein that contains two bromodomains, sequence motifs of unknown function. Separation-of-function alleles suggest that only one of the two bromodomains is required for sporulation, whereas both are required for Bdf1 function in vegetative cells. We propose that the Bdf1 protein is a component of chromatin and that the mitotic and meiotic defects of the bdf1 null mutant result from alterations in chromatin structure.

Segregation of recombinant chromatids following mitotic crossing over in yeast.

It has long been assumed that chromatid segregation following mitotic crossing over in yeast is random, with the recombinant chromatids segregating to opposite poles of the cell (x-segregation) or to the same pole of the cell (z-segregation) with equal frequency. X-segregation events can be readily identified because heterozygous markers distal to the point of the exchange are reduced to homozygosity. Z-segregation events yield daughter cells which are identical phenotypically to nonrecombinant cells and thus can only be identified by the altered linkage relationships of genetic markers on opposite sides of the exchange. We have systematically examined the segregation patterns of chromatids with a spontaneous mitotic exchange in the CEN5-CAN1 interval on chromosome V. We find that the number of x-segregation events is equal to the number of z-segregations, thus demonstrating that chromatid segregation is indeed random. In addition, we have found that at least 5% of the cells selected for a recombination event on chromosome V are trisomic for this chromosome, indicating a strong association between mitotic recombination and chromosome nondisjunction.

Nucleotide excision repair genes are upregulated by low-dose artificial ultraviolet B: evidence of a photoprotective SOS response?

Nucleotide excision repair is a major mechanism of defense against the carcinogenic effects of ultraviolet light. Ultraviolet B causes sunburn and DNA damage in human skin. Nucleotide excision repair has been studied extensively and described in detail at the molecular level, including identification of many nucleotide excision repair-specific proteins and the genes encoding nucleotide excision repair proteins. In this study, normal human keratinocytes were exposed to increasing doses of ultraviolet B from fluorescent sunlamps, and the effect of this exposure on expression of nucleotide excision repair genes was examined. An RNase protection assay was performed to quantify transcripts from nucleotide excision repair genes, and a slot blot DNA repair activity assay was used to assess induction of the nucleotide excision repair pathway. The activity assay demonstrated that cyclobutane pyrimidine dimers were removed efficiently after exposure to low doses of ultraviolet B, but this activity was delayed significantly at higher doses. All nucleotide excision repair genes examined demonstrated a similar trend: ultraviolet B induces expression of nucleotide excision repair genes at low doses, but downregulates expression at higher doses. In addition, we show that pre-exposure of cells to low-dose ultraviolet protected keratinocytes from apoptosis following high-dose exposure. These data support the notion that nucleotide excision repair is induced in cells exposed to low doses of ultraviolet B, which may protect damaged keratinocytes from cell death; however, exposure to high doses of ultraviolet B downregulates nucleotide excision repair genes and is associated with cell death.

Common effects of emotional valence, arousal and attention on neural activation during visual processing of pictures.

Emotion and attention heighten sensitivity to visual cues. How neural activation patterns associated with emotion change as a function of the availability of attentional resources is unknown. We used positron emission tomography (PET) and 15O-water to measure brain activity in male volunteers while they viewed emotional picture sets that could be classified according to valence or arousal. Subjects simultaneously performed a distraction task that manipulated the availability of attentional resources. Twelve scan conditions were generated in a 3 x 2 x 2 factorial design involving three levels of valence (pleasant, unpleasant and neutral), two levels of arousal and two levels of attention (low and high distraction). Extrastriate visual cortical and anterior temporal areas were independently activated by emotional valence, arousal and attention. Common areas of activation derived from a conjunction analysis of these separate activations revealed extensive areas of activation in extrastriate visual cortex with a focus in right BA18 (12, -88, -2) (Z=5.73, P < 0.001 corrected) and right anterior temporal cortex BA38 (42, 14, -30) (Z=4.03, P < 0.05 corrected). These findings support an hypothesis that emotion and attention modulate both early and late stages of visual processing.

Lack of association between acquisition of TT virus and risk behavior for HIV and HCV infection in Vietnam.

BACKGROUND: The search for the cause of chronic hepatitis among individuals with non-A to G hepatitis has led to the discovery of a post-transfusion hepatitis-related DNA virus, designated TT virus (TTV), which, based on viral sequences, belongs to a new virus family. The principal modes of infection with TTV are poorly understood, and its role in human immunodeficiency virus type 1 (HIV-1) infection is unclear. OBJECTIVE: To determine if injection drug use (IDU) and high-risk heterosexual activity (HRHA), principal modes of acquiring HIV-1 infection, place individuals at greater risk of acquiring TTV. METHODS: The authors analyzed DNA, extracted from sera or filter paper-blotted whole blood, obtained during August 1997 and June 1998 from 324 Vietnamese (148 male; 176 female), for TTV sequences by hot-start, heminested polymerase chain reaction. RESULTS: Prevalence of TTV viremia was similar among individuals engaging in IDU or HRHA (23.4% vs. 20.2%; P > 0.5), with no age- or gender-specific differences. No association was found between TTV viremia and co-infection with HIV-1 or hepatitis C virus (HCV). Phylogenetic analysis of 30 TTV sequences revealed two distinct genotypes and four subtypes that did not segregate according to gender, HIV-1 and HCV risk behaviors, or geographic residence. CONCLUSIONS: Among HIV-1- or HCV-infected Vietnamese, who presumably acquired their infection by either the parenteral or nonparenteral route, the data indicate no clear association between acquisition of TTV infection and risk behavior for HIV-1 or HCV infection, suggesting that the usual route of TTV transmission in Vietnam is other than parenteral or sexual.

Gradual loss of IgG antibodies against GB virus C/hepatitis G virus in a patient with AIDS.

GB virus C/hepatitis G virus (GBV-C/HGV) is a positive-sense, single-stranded RNA virus belonging to the family Flaviviridae and is distantly related to hepatitis C virus (HCV). GBV-C/HGV can be transmitted by the parenteral and the sexual route. Among individuals infected with human immunodeficiency virus type 1 (HIV-1) by the sexual route, we and others have demonstrated a high prevalence of GBV-C/HGV infection. Recently, Woolley and colleagues reported that AIDS patients co-infected with GBV-C/HGV had a significantly lower mean CD4 cell count than AIDS patients without GBV-C/HGV infection, suggesting that GBV-C/HGV antibody may be lost with progression to AIDS. To our knowledge no data are available on the loss of antibody against GBV-C/HGV in AIDS patients. We now report on an HIV-infected patient who exhibited gradual loss of IgG antibodies against GBV-C/HGV, as well as HCV, with progression of HIV disease.

Prefrontal activity in Huntington's disease reflects cognitive and neuropsychiatric disturbances: the IMAGE-HD study.

Functional integrity of prefrontal cortico-striatal circuits underlying executive functioning may be compromised by basal ganglia degeneration during Huntington's disease (HD). This study investigated challenged inhibitory attentional control with a shifting response-set (SRS) task whilst assessing neural response via functional magnetic resonance imaging (fMRI) in 35 healthy controls, 35 matched pre-symptomatic (pre-HD) and 30 symptomatic (symp-HD) participants. A ≥70% performance accuracy threshold allowed confident identification of neural activity associated with SRS performance in a sub-set of 33 healthy controls, 32 pre-HD and 20 symp-HD participants. SRS activated dorsolateral prefrontal and dorsal anterior cingulate cortices, premotor, parietal, and basal ganglia regions and deactivated subgenual anterior cingulate cortex. Symp-HD participants showed greater prefrontal functional responses relative to controls and pre-HD, including larger activations and larger deactivations in response to cognitive challenge, consistent with compensatory neural recruitment. We then investigated associations between prefrontal BOLD responses, SRS performance accuracy and neuropsychiatric disturbance in all participants, including those below SRS performance accuracy threshold. We observed that reduced prefrontal responsivity in symp-HD was associated with reduced accuracy in SRS performance, and with increased neuropsychiatric disturbance within domains including executive dysfunction, pathological impulses, disinhibition, and depression. These findings demonstrate prefrontal response during inhibitory attentional control usefully characterises cognitive and neuropsychiatric status in symp-HD. The functional integrity of compensatory prefrontal responses may provide a useful marker for treatments which aim to sustain cognitive function and delay executive and neuropsychiatric disturbance.

Ministry of Health clinical practice guidelines: depression.

The Ministry of Health (MOH) have updated the clinical practice guidelines on Depression to provide doctors and patients in Singapore with evidence-based treatment for depression. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Depression, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/home/Publications/guidelines/cpg/2012/depression.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Structural stability and bioapplicability assessment of hyaluronic acid-chitosan polyelectrolyte multilayers on titanium substrates.

Since bacterial infections associated with implants remain a major cause of their failure, this study investigated the use of polyelectrolyte multilayers (PEMs) comprising hyaluronic acid (HA) and chitosan (CH) to confer antibacterial properties on titanium (Ti). HA and CH were deposited on Ti using the layer-by-layer deposition method. The antibacterial efficacy of the functionalized Ti substrates was assessed using Escherichia coli and Staphylococcus aureus. The number of adherent bacteria on Ti functionalized with HA and CH PEMs was up to an order of magnitude lower than that on the pristine Ti. The effects of chemical crosslinking of the PEMs on the structural stability and antibacterial efficacy were investigated. The chemical crosslinking of the PEMs imparts greater structural stability and preserves the antibacterial properties even after the prolonged immersion in phosphate-buffered saline. The cytotoxicity of the PEMs to osteoblasts was evaluated using the MTT assay. The results showed that the biocompatible and long-lasting antibacterial nature of the functionalized Ti substrates offers great potential for reducing implant-associated infections.

Depression and neurocognitive performance in individuals with HIV/AIDS: 2-year follow-up.

OBJECTIVES: The aims of this study were to follow a cohort of HIV-infected individuals for 2 years to assess changes in depression and neuropsychological performance over time, to explore the relationship between depression, HIV illness and neuropsychological performance, and to examine the natural history of the effect of highly active antiretroviral therapy (HAART) on depression and neurocognitive performance. METHODS: HIV-seropositive out-patients were assessed at baseline and at 2-year follow-up. At each assessment, patients were assessed for depression [using the Beck Depression Inventory (BDI) and Structured Clinical Interview (SCID-CV)] and completed a battery of neuropsychological tests including the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Hopkins HIV Dementia Scale (HDS). RESULTS: At baseline, 34.8% scored > or =14 on the BDI [> or =14 suggests depressive symptoms (DS)]. The SCID-CV revealed that 27% of participants met the criteria for current mood disorder. Seven per cent of the participants' scores on the HDS indicated HIV-associated cognitive changes. Eighty participants were re-tested at 2-year follow-up and were split into two groups based on BDI scores at baseline. CANTAB results revealed that the cohort were significantly impaired on nine of 10 measures compared with age-matched normative data. Neurocognitive performance significantly improved for participants with no DS at baseline, whereas participants with DS at baseline did not show as much improvement. Multivariate analysis revealed that 40% of the change in cognitive performance was attributable to the variables age, AIDS and HAART regimen. CONCLUSION: These results suggest a significant decline in depression scores and an improvement in several neurocognitive domains over time, with a relationship between HIV illness, HAART, symptoms of depression and neurocognitive performance.

Zip2, a meiosis-specific protein required for the initiation of chromosome synapsis.

We describe the identification and characterization of the Saccharomyces cerevisiae ZIP2 gene, which encodes a novel meiosis-specific protein essential for synaptonemal complex formation. In the zip2 mutant, chromosomes are homologously paired but not synapsed. The Zip2 protein localizes to discrete foci on meiotic chromosomes; these foci correspond to sites of convergence between paired homologs that are believed to be sites of synapsis initiation. Localization of Zip2p requires the initiation of meiotic recombination. In a mutant defective in double-strand break repair, Zip2p colocalizes with proteins involved in double-strand break formation and processing. We propose that Zip2p promotes the initiation of chromosome synapsis and that localization of Zip2p to sites of interhomolog recombination ensures synapsis between homologous chromosomes.