Cenicriviroc, a dual CCR2 and CCR5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with HIV on antiretroviral therapy.

Background: Chronic HIV is associated with increased inflammation and tissue fibrosis despite suppressive antiretroviral therapy (ART). Monocytes and macrophages have been implicated in the pathogenesis of fibrosis, facilitated by chemokine receptor interactions.Methods: We assessed systemic fibrotic biomarkers (transforming growth factor beta-1 [TGF-ß1], thrombospondin-1 [TSP-1], C-terminal pro-peptide of collagen type I [CICP], and IL-11) in banked plasma from a previously published 24-week open-label trial of cenicriviroc (CVC), a dual CCR2/CCR5 antagonist, among persons living with HIV (PLWH) on stable ART with undetectable plasma HIV RNA (<50 copies/mL). Fibrotic markers were assessed by ELISA and Luminex. Untreated HIV-seronegative individuals (n = 6) of similar age and demographics served as a comparator group.Results: Median age of PLWH was 55 years. At baseline, PLWH had higher median TGF-ß1 (2.11 vs 1.62 ng/mL, p = 0.01), TSP-1 (236.74 vs 83.29 ng/mL, p < 0.0001), and CICP (200.46 vs 111.28 ng/mL, p = 0.01), but lower IL-11 (36.00 vs 53.74 pg/mL, p = 0.01) compared to HIV-uninfected individuals. Over 24 weeks, median TGF-ß1 (-0.74 ng/mL, p = 0.006), TSP-1 (-52.12 ng/mL, p < 0.0001), and CICP (-28.12 ng/mL, p < 0.0001) decreased and IL-11 (28.98 pg/mL, p < 0.0001) increased in PLWH. At week 24, TGF-ß1, CICP, and IL-11 were similar between the two groups (p > 0.05), while TSP-1 remained elevated in PLWH (p = 0.009) compared to controls.Conclusions: PLWH had higher levels of the plasma fibrotic markers TGF-ß1, TSP-1, and CICP. After 24 weeks of CVC, fibrotic markers generally returned to levels comparable to HIV-uninfected controls. Dual CCR2 and CCR5 blockade may ameliorate the detrimental fibrotic events that persist in treated HIV.

What the child "SAID" to the dentist: A UK randomized controlled trial.

BACKGROUND: The electronic Survey of Anxiety and Information for Dentists (eSAID) allows children to tell dentists about their feelings and coping preferences. It is a computer "quiz" with 26 questions and free-text responses that produces a report for the children that they can then hand to their dentist. This is the first study to report the use of eSAID in a hospital paediatric dental clinic. METHODS: This was a randomized controlled trial to evaluate whether children thought that eSAID benefitted them, made them less anxious, and improved cooperation and their treatment satisfaction. Fifty-one children aged 8-13 years were randomized to complete either eSAID or a control version in the waiting room before their scheduled dental appointment. The study group had a 26-item questionnaire; the control had only two items. Both groups scored their anxiety on a 7-point anxiety scale at the start and again at the end of the quiz. All subjects handed the resultant eSAID report as a printout to their dentist. Dental treatment proceeded as planned. After treatment, each child reported how they thought the eSAID quiz had benefitted them by scoring on a 10 cm Visual Analogue Scale and their satisfaction on the Modified Treatment Evaluation Inventory. The operating dentists scored the children's cooperation using a 10 cm Visual Analogue Scale. RESULTS: Overall, the baseline anxiety levels were low (study: mean 1.2; control: mean 1.5). The study group's post-survey anxiety reduced by 0.4, whereas controls' increased by 0.2; this difference is statistically significant (p = .04). However, it made no difference to the children's self-reported benefit (p = .30), satisfaction (p > .05), or cooperation (p = .34). CONCLUSIONS: eSAID reduced pre-treatment anxiety but made no difference to children's perceived benefit, satisfaction, or cooperation. Future study should include known anxious children.

Identification of Caries Risk Determinants in Toddlers: Results of the GUSTO Birth Cohort Study.

The aim of this study was to identify risk determinants leading to early childhood caries (ECC) and visible plaque (VP) in toddlers. Data for mother-child pairs participating in the Growing Up in Singapore towards Healthy Outcomes (GUSTO) birth cohort were collected from pregnancy to toddlerhood. Oral examinations were performed in 543 children during their clinic visit at 24 months to detect ECC and VP. Following logistic regression, ECC and VP were jointly regressed as primary and secondary outcomes, respectively, using the bivariate probit model. The ECC prevalence was 17.8% at 2 years of age, with 7.3% of children having a VP score >1. ECC was associated with nighttime breastfeeding (3 weeks) and biological factors, including Indian ethnicity (lower ECC rate), higher maternal childbearing age and existing health conditions, maternal plasma folate <6 ng/mL, child BMI, and the plaque index, while VP was associated with psychobehavioral factors, including the frequency of dental visits, brushing frequency, lower parental perceived importance of baby teeth, and weaning onto solids. Interestingly, although a higher frequency of dental visits and toothbrushing were associated with lower plaque accumulation, they were associated with increased ECC risk, suggesting that these established caries-risk factors may be a consequence rather than the cause of ECC. In conclusion, Indian toddlers may be less susceptible to ECC, compared to Chinese and Malay toddlers. The study also highlights a problem-driven utilization pattern of dental services (care sought for treatment) in Singapore, in contrast to the prevention-driven approach (care sought to prevent disease) in Western countries.

Limit on Tensor Currents from

In the standard model, the weak interaction is formulated with a purely vector-axial-vector (V-A) structure. Without restriction on the chirality of the neutrino, the most general limits on tensor currents from nuclear ß decay are dominated by a single measurement of the ß-ν[over ¯] correlation in ^{6}He ß decay dating back over a half century. In the present work, the ß-ν[over ¯]-α correlation in the ß decay of ^{8}Li and subsequent α-particle breakup of the ^{8}Be^{*} daughter was measured. The results are consistent with a purely V-A interaction and in the case of couplings to right-handed neutrinos (C_{T}=-C_{T}^{'}) limits the tensor fraction to |C_{T}/C_{A}|^{2}<0.011 (95.5% C.L.). The measurement confirms the ^{6}He result using a different nuclear system and employing modern ion-trapping techniques subject to different systematic uncertainties.

Risk score algorithm for treatment of persistent apical periodontitis.

Persistent apical periodontitis related to a nonvital tooth that does not resolve following root canal treatment may be compatible with health and may not require further intervention. This research aimed to develop a Deterioration Risk Score (DRS) to differentiate lesions requiring further intervention from lesions likely to be compatible with health. In this cross-sectional study, patient records (2003-2008) were screened for root-filled teeth with periapical radiolucency visible on periapical radiographs taken at treatment and at recruitment at least 4 yr later. The final sample consisted of 228 lesions in 182 patients. Potential demographic and treatment risk factors were screened against 3 categorical outcomes (improved/unchanged/deteriorated), and a multivariate independent multinomial probit regression model was built. A 5-level DRS was constructed by summing values of adjusted regression coefficients in the model, based on predicted probabilities of deterioration. Most lesions (127, 55.7%) had improved over time, while 32 (14.0%) remained unchanged, and 69 (30.3%) had deteriorated. Significant predictors of deterioration were as follows: time since treatment (relative risk [RR]: 1.11, 95% confidence interval [CI]: 1.01-1.22, p = .030, rounded beta value = 1, for every year increase after 4 yr), current pain (RR: 3.79, 95% CI: 1.48-9.70, p = .005, rounded beta value = 13), sinus tract present (RR: 4.13, 95% CI: 1.11-15.29, p = .034, rounded beta value = 14), and lesion size (RR: 7.20, 95% CI: 3.70-14.02, p < .001, rounded beta value = 20). Persistent apical periodontitis with DRS <15 represented very low risk; 15-20, low risk; 21-30, moderate risk; 31-40, high risk; and >40, very high risk. DRS could help the clinician identify persistent apical periodontitis at low risk for deterioration, and it would not require intervention. When validated, this tool could reduce the risk of overtreatment and contribute toward targeted care and better efficiency in the timely management of disease.

ß-delayed neutron spectroscopy using trapped radioactive ions.

A novel technique for ß-delayed neutron spectroscopy has been demonstrated using trapped ions. The neutron-energy spectrum is reconstructed by measuring the time of flight of the nuclear recoil following neutron emission, thereby avoiding all the challenges associated with neutron detection, such as backgrounds from scattered neutrons and γ rays and complicated detector-response functions. (137)I(+) ions delivered from a (252)Cf source were confined in a linear Paul trap surrounded by radiation detectors, and the ß-delayed neutron-energy spectrum and branching ratio were determined by detecting the ß(-) and recoil ions in coincidence. Systematic effects were explored by determining the branching ratio three ways. Improvements to achieve higher detection efficiency, better energy resolution, and a lower neutron-energy threshold are proposed.

Tensor interaction limit derived from the α-ß-ν[over ¯] correlation in trapped 8Li ions.

A measurement of the α-ß-ν[over ¯] angular correlation in the Gamow-Teller decay (8)Li→(8)Be(*)+ν[over ¯]+ß, (8)Be(*)→α+α has been performed using ions confined in a linear Paul trap surrounded by silicon detectors. The energy difference spectrum of the α particles emitted along and opposite the direction of the ß particle is consistent with the standard model prediction and places a limit of 3.1% (95.5% confidence level) on any tensor contribution to the decay. From this result, the amplitude of any tensor component C(T) relative to that of the dominant axial-vector component C(A) of the electroweak interaction is limited to |C(T)/C(A)|<0.18 (95.5% confidence level). This experimental approach is facilitated by several favorable features of the (8)Li ß decay and has different systematic effects than the previous ß-ν[over ¯] correlation results for a pure Gamow-Teller transition obtained from studying (6)He ß decay.

Measurement of excitation functions for the (nat)Mo(d,x)99Mo and (nat)Mo(p,x)99Mo reactions.

The excitation functions for proton and deuteron induced reactions on natural molybdenum for the production of 99Mo were measured. The proton induced reaction was measured in the energy range of 11.3-49.6 MeV, and the deuteron induced reaction was measured in the energy range of 9.7-58.5 MeV. Both beams were generated by the 88" cyclotron located at Lawrence Berkeley National Laboratory. The results are compared to previously published data. Thick target yields were obtained by direct measurement, in addition to being determined by integration of the measured cross sections.

Health Promotion Board-Ministry of Health clinical practice guidelines: functional screening for older adults in the community.

The Health Promotion Board (HPB) and the Ministry of Health (MOH) publish clinical practice guidelines to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the HPB-MOH clinical practice guidelines on Functional Screening for Older Adults in the Community, 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 Health Promotion Board website (http://www.hpb.gov.sg/uploadedFiles/HPB_Online/Publications/CPGFunctionalscreening.pdf). 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.

Efficacy of silver diamine fluoride for Arresting Caries Treatment.

Arresting Caries Treatment (ACT) has been proposed to manage untreated dental caries in children. This prospective randomized clinical trial investigated the caries-arresting effectiveness of a single spot application of: (1) 38% silver diamine fluoride (SDF) with tannic acid as a reducing agent; (2) 38% SDF alone; (3) 12% SDF alone; and (4) no SDF application in primary teeth of 976 Nepalese schoolchildren. The a priori null hypothesis was that the different treatments have no effect in arresting active cavitated caries. Only the single application of 38% SDF with or without tannic acid was effective in arresting caries after 6 months (4.5 and 4.2 mean number of arrested surfaces; p < 0.001), after 1 year (4.1 and 3.4; p < 0.001), and after 2 years (2.2 and 2.1; p < 0.01). Tannic acid conferred no additional benefit. ACT with 38% SDF provides an alternative when restorative treatment for primary teeth is not an option.

A global perspective on changes in the burden of caries and periodontitis: implications for dentistry.

The structure and contents of most oral health care systems and the contents of dental curricula reflect a deep-rooted tradition for attempting to cure oral diseases by refined technological means. However, better oral health conditions for the world's populations necessitate the application of up-to-date scientific knowledge to control the major oral diseases. This review points out that not only should the structure and contents of oral health care delivery systems be based on state-of-the-art knowledge about the biology of the oral diseases; they must also take into account the trends for change in caries and periodontal diseases within and between populations, and acknowledge the impact of changes in treatment philosophies for these trends. The oral disease profiles for populations in low- and high-income countries are briefly described, and it is concluded that the rapidly changing disease profiles observed in high-income countries necessitate re-thinking of the future role and organization of dentistry in such countries. The priorities for low- and middle-income countries must be to avoid repeating the mistakes made in the high-income countries. Instead, these societies might take advantage of setting priorities based on a population-based common risk factor approach. If such an approach is adopted, the training of personnel with oral health care competence must be rethought. The authors suggest three different cadres of dental care providers to be considered for an approach that allows health care planners in different populations around the world to prioritize appropriate oral health care with due respect for the socio-economic conditions prevailing.

Oral cleanliness of 12-13-year-old and 15-year-old school children of Sunsari District, Nepal.

The aim of the study was to evaluate the oral cleanliness of school children in the District of Sunsari, Nepal. A multi-stage random sampling oral epidemiological survey was conducted in private and government, urban, rural town and rural village schools in 15 illakas of Sunsari District, Eastern Nepal. A total of 600, 12-13-year-old and 600 15-year-old school children were examined by trained examiners using the simplified oral hygiene index (OHI-S). The average age-group, debris and calculus index scores were combined to obtain the simplified oral hygiene index (OHI-S). The mean OHI-S scores were compared and evaluated using the parametric t-test for two independent samples. The mean OHI-S for urban 12-13-year-old school children was 0.98 compared to 1.34 for school children of rural towns and 1.44 for school children of rural villages and these differences in mean OHI-S were statistically significant (P < 0.005). In the 15-year-old age group, urban school children had a mean OHI-S score of 1.00 compared to 1.37 for rural towns and 1.43 for rural villages. The variance in the mean OHI-S scores were statistically significant (P < 0.005). The overall level of cleanliness in the school children surveyed was good. Children of urban schools had the lowest scores followed by school children from rural towns and then rural villages. When the mean OHI-S scores were compared with the DMFT scores, there was an inverse relationship between oral cleanliness and dental caries. Frequency of sugar consumption and the availability and affordability of fluoridated toothpaste may be important factors in the development of dental caries than oral cleanliness.

Saccades in presymptomatic and early stages of Huntington disease.

OBJECTIVE: To evaluate quantitative measures of eye movements as possible biomarkers in prediagnostic and early stages of Huntington disease (HD). METHODS: The study sample (n = 215) included individuals both at risk and recently diagnosed with HD. All participants completed a uniform clinical evaluation which included administration of the Unified Huntington's Disease Rating Scale (UHDRS) by a movement disorder neurologist and molecular testing to determine HD gene status. A high resolution, video-based eye tracking system was employed to quantify measures of eye movement (error rates, latencies, SD of latencies, velocities, and accuracies) during a computerized battery of saccadic and steady fixation tasks. RESULTS: Prediagnostic HD gene carriers and individuals with early HD demonstrated three types of significant abnormalities while performing memory guided and anti-saccade tasks: increased error rate, increased saccade latency, and increased variability of saccade latency. The eye movement abnormalities increased with advancing motor signs of HD. CONCLUSIONS: Abnormalities in eye movement measures are a sensitive biomarker in the prediagnostic and early stages of Huntington disease (HD). These measures may be more sensitive to prediagnostic changes in HD than the currently employed neurologic motor assessment.

Health-related quality of life relative to clinical outcomes in patients with atrial fibrillation treated with ventricular rate stabilisation pacing.

AIMS: It is uncertain whether patient perception of atrial fibrillation (AF) is based on the fast ventricular rate as such or the irregularity of the ventricular responses. This trial was designed to confirm the effectiveness of a ventricular rate stabilisation (VRS) algorithm in reducing ventricular irregularity during permanent pacing in patients with AF and to assess the patient preference and effect on quality of life (QoL). METHODS: In this multicentre single-blind randomised crossover trial, 184 patients with drug-refractory permanent (n=91) or paroxysmal (n=93) AF received a VVI(R) or DDD(R) pacemaker respectively and were paced in a randomised sequence with VRS on or off for two months. Clinical assessments (QoL, New York Heart Association (NYHA) classification, echocardiography, six-minute walk test and Holter recording) were carried out at baseline, at randomisation and after each crossover period. QoL assessment was performed using Aquarel, a new disease-specific QoL questionnaire for pacemaker patients, the Short Form 36 survey (SF-36), the Duke Activity Status Index (DASI) and the Symptom Checklist frequency and severity scores. At the end of the study patients preferences for VRS-on or VRS-off were recorded. RESULTS: VRS pacing reduced ventricular irregularity without increasing the mean ventricular rate. VRS-on was preferred by 65.8% of patients with paroxysmal AF; patients with permanent AF had no preference. QoL did not show improvement during VRS pacing on any of the instruments. CONCLUSION: VRS pacing is effective in reducing ventricular rhythm irregularity. QoL does not improve during VRS pacing but preference for VRS pacing appears particularly outspoken for patients with paroxysmal AF.

Use of medications in Wolff-Parkinson-White syndrome.

The diagnosis of Wolff-Parkinson-White syndrome is generally straightforward; however, the management may not be, and requires an understanding of the competing risks of various treatment options and that of the clinical setting in which the diagnosis is made. The symptomatic patient with Wolff-Parkinson-White has an increased risk of atrial fibrillation and a small but significant risk of sudden cardiac death. Therapy is based on reduction in symptom burden and attenuation of the risk of pre-excited atrial fibrillation. Catheter ablation is the most effective means of achieving this goal with abolition of symptoms and risk of pre-excited atrial fibrillation. Medication is often employed in the acute setting to terminate paroxysms of arrhythmia associated with the accessory pathway and reduce the subsequent burden of symptoms until ablation can be performed. An overview of the agents commonly used is provided together with recommendations.

Oculomotor control in asymptomatic and recently diagnosed individuals with the genetic marker for Huntington's disease.

We compared oculomotor control among individuals in the early stages of Huntington's disease (HD), with that of individuals who are presymptomatic HD gene carriers (PSGC) and nongene carriers (NGC). The oculomotor testing paradigm included both traditional tests and a novel experimental procedure to assess visual scanning. Traditional tests elicited saccades, pursuit and optokinetic nystagmus (OKN). HD patients demonstrated marked delay in the initiation of volitional saccades (anti-saccade and memory-guided saccades), a reduced number of correct volitional saccades, reduced velocity of saccades, and a decreased OKN gain. We also studied visual scanning while the participants completed the Digit Symbol Subscale of the Wechsler Adult Intelligence Survey-Revised (WAIS-R). The HD participants demonstrated an abnormal gaze strategy, which may be associated with attention and/or planning deficits. Differences between the PSGC and NGC groups were only observed for two measures: PSGC had a decreased number of memory-guided saccades and a subtle delay in the initiation of volitional saccades. Our results suggest that oculomotor measures are a sensitive biomarker in the early stage of HD and demonstrate that the combination of more traditional oculomotor tests with visual scanning tests is useful in the evaluation of visual performance.

An advocacy project to fluoridate toothpastes in Nepal.

AIMS: To describe a recent health promotion project undertaken by the United Mission to Nepal Oral Health Programme (UMN OHP) to increase the availability and consumption of affordable, fluoridated toothpaste in Nepal. METHOD: The process of advocating for the fluoridation of toothpastes in Nepal is based on Tearfund's advocacy cycle. RESULTS: The project achieved health promotion outcomes including healthy corporate and public policies and organisational practice and intermediate outcomes such as increased availability and consumption of affordable fluoridated toothpaste. Prior to implementation of the advocacy project in 1997, availability and consumption of fluoridated toothpaste was negligible. By March 2002 total market share of fluoridated toothpaste was approximately 90%. This represents an annual tonnage of 900 tons of fluoridated toothpaste. CONCLUSIONS: The health promotion activity of advocacy for the fluoridation of toothpastes in Nepal achieved measurable gains in health promotion outcomes and intermediate outcomes. Gains in health and social outcomes will take longer to evaluate but based on epidemiological evidence and the experience of other countries increased availability of affordable fluoridated toothpaste will have a significant and ongoing impact on the oral health of the people of Nepal.