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This study evaluates contributions of jaw injury and experimental pain sensitivity to risk of developing painful temporomandibular disorder (TMD). Data were from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) nested case-control study of incident painful TMD. Injury and subsequent onset of painful TMD were monitored prospectively for ≤5 y in a community-based sample of 409 US adults who did not have TMD when enrolled. At baseline, thermal-pressure and pinprick pain sensitivity, as potential effect modifiers, were measured using quantitative sensory testing. During follow-up, jaw injury from any of 9 types of potentially traumatic events was determined using quarterly (3-monthly) health update questionnaires. Study examiners classified incident painful TMD, yielding 233 incident cases and 176 matched controls. Logistic regression models, estimated incidence odds ratios (IORs), and 95% confidence limits (CLs) were used for the association between injury and subsequent onset of painful TMD. During follow-up, 38.2% of incident cases and 13.1% of controls reported 1 or more injuries that were 4 times as likely to be intrinsic (i.e., sustained mouth opening or yawning) as extrinsic (e.g., dental visits, whiplash). Injuries due to extrinsic events (IOR = 7.6; 95% CL, 1.6-36.2), sustained opening (IOR = 5.4; 95% CL, 2.4-12.2), and yawning (IOR = 3.4; 95% CL, 1.6-7.3) were associated with increased TMD incidence. Both a single injury (IOR = 6.0; 95% CL, 2.9-12.4) and multiple injuries (IOR = 9.4; 95% CL, 3.4,25.6) predicted greater incidence of painful TMD than events perceived as noninjurious (IOR = 1.9; 95% CL, 1.1-3.4). Injury-associated risk of painful TMD was elevated in people with high sensitivity to heat pain (IOR = 7.4; 95% CL, 3.1-18.0) compared to people with low sensitivity to heat pain (IOR = 3.9; 95% CL, 1.7-8.4). Jaw injury was strongly associated with elevated painful TMD risk, and the risk was amplified in subjects who had enhanced sensitivity to heat pain at enrollment. Commonly occurring but seemingly innocuous events, such as yawning injury, should not be overlooked when judging prognostic importance of jaw injury. [ABSTRACT FROM AUTHOR]

The chemical, bioactive, and antioxidant potential of twenty wild culinary mushroom species being consumed by the people of northern Himalayan regions has been evaluated for the first time in the present study. Nutrients analyzed include protein, crude fat, fibres, carbohydrates, and monosaccharides. Besides, preliminary study on the detection of toxic compounds was done on these species. Bioactive compounds evaluated are fatty acids, amino acids, tocopherol content, carotenoids (β-carotene, lycopene), flavonoids, ascorbic acid, and anthocyanidins. Fruitbodies extract of all the species was tested for different types of antioxidant assays. Although differences were observed in the net values of individual species all the species were found to be rich in protein, and carbohydrates and low in fat. Glucose was found to be the major monosaccharide. Predominance of UFA (65–70%) over SFA (30–35%) was observed in all the species with considerable amounts of other bioactive compounds. All the species showed higher effectiveness for antioxidant capacities. [ABSTRACT FROM AUTHOR]

The canonical wingless-type MMTV integration site (WNT)-β-catenin pathway is essential for self-renewal, growth and survival of acute myeloid leukemia (AML) stem/blast progenitor cells (BPCs). Deregulated WNT signaling inhibits degradation of β-catenin, causing increased nuclear translocation and co-factor activity of β-catenin with the transcriptional regulator T-cell factor (TCF) 4/lymphoid enhancer factor 1 in AML BPCs. Here, we determined the pre-clinical anti-AML activity of the anthraquinone oxime-analog BC2059 (BC), known to attenuate β-catenin levels. BC treatment disrupted the binding of β-catenin with the scaffold protein transducin β-like 1 and proteasomal degradation and decline in the nuclear levels of β-catenin. This was associated with reduced transcriptional activity of TCF4 and expression of its target genes, cyclin D1, c-MYC and survivin. BC treatment dose-dependently induced apoptosis of cultured and primary AML BPCs. Treatment with BC also significantly improved the median survival of immune-depleted mice engrafted with either cultured or primary AML BPCs, exhibiting nuclear expression of β-catenin. Co-treatment with the pan-histone deacetylase inhibitor panobinostat and BC synergistically induced apoptosis of cultured and primary AML BPCs, including those expressing FLT3-ITD, as well as further significantly improved the survival of immune-depleted mice engrafted with primary AML BPCs. These findings underscore the promising pre-clinical activity and warrant further testing of BC against human AML, especially those expressing FLT3-ITD. [ABSTRACT FROM AUTHOR]

Background Traditionally, the Arctic diet has been derived entirely from locally harvested animal and plant species; however, in recent decades, imported foods purchased from grocery stores have become widely available. The present study aimed to examine Inuvialuit, traditional or nontraditional dietary patterns; nutrient density of the diet; dietary adequacy; and main food sources of energy and selected nutrient intakes. Methods This cross-sectional study used a culturally appropriate quantitative food frequency questionnaire to assess diet. Traditional and nontraditional eaters were classified as those consuming more or less than 300 g of traditional food daily. Nutrient densities per 4184 kJ (1000 kcal) were determined. Dietary adequacy was determined by comparing participants' nutrient intakes with the Dietary Reference Intakes. Results The diet of nontraditional eaters contained, on average, a lower density of protein, niacin, vitamin B12, iron, selenium, zinc, omega-3 fatty acids ( P ≤ 0.0001), vitamin B6, potassium, thiamin, pantothenic acid ( P ≤ 0.001), riboflavin and magnesium ( P ≤ 0.05). Inadequate nutrient intake was more common among nontraditional eaters for calcium, folate, vitamin C, zinc, thiamin, pantothenic acid, vitamin K, magnesium, potassium and sodium. Non-nutrient-dense foods (i.e. high fat and high sugar foods) contributed to energy intake in both groups, more so among nontraditional eaters (45% versus 33%). Traditional foods accounted for 3.3% and 20.7% of total energy intake among nontraditional and traditional eaters, respectively. Conclusions Diet quality and dietary adequacy were better among Inuvialuit who consumed more traditional foods. The promotion of traditional foods should be incorporated in dietary interventions for this population. [ABSTRACT FROM AUTHOR]

Objectives The risks and benefits of initiating antiretroviral treatment ( ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment ( START) study is a randomized international clinical trial that compares immediate with deferred initiation of ART for HIV-positive individuals with CD4 cell counts above 500 cells/μL. We describe the demographics, HIV-specific characteristics and medical history of this cohort. Methods Data collected at baseline include demographics, HIV-specific laboratory values, prior medical diagnoses and concomitant medications. Baseline characteristics were compared by geographical region, gender and age. Results START enrolled 4685 HIV-positive participants from 215 sites in 35 countries. The median age is 36 years [interquartile range ( IQR) 29-44 years], 27% are female, and 45% self-identify as white, 30% as black, 14% as Latino/Hispanic, 8% as Asian and 3% as other. The route of HIV acquisition is reported as men who have sex with men in 55% of participants, heterosexual sex in 38%, injecting drug use in 1% and other/unknown in 5%. Median time since HIV diagnosis is 1.0 year ( IQR 0.4-3.0 years) and the median CD4 cell count and HIV RNA values at study entry are 651 cells/μL ( IQR 584-765 cells/μL) and 12 754 HIV RNA copies/mL ( IQR 3014-43 607 copies/mL), respectively. Conclusions START has enrolled a diverse group of ART-naïve individuals with high CD4 cell counts who are comparable to the HIV-positive population from the regions in which they were enrolled. The information collected with this robust study design will provide a database with which to evaluate the risks and benefits of early ART use for many important outcomes. [ABSTRACT FROM AUTHOR]

Objectives The Strategic Timing of AntiRetroviral Treatment ( START) trial has recruited antiretroviral-naïve individuals with high CD4 cell counts from all regions of the world. We describe the distribution of cardiovascular disease ( CVD) risk factors, overall and by geographical region, at study baseline. Methods The distribution of CVD risk factors was assessed and compared by geographical region among START participants who had a baseline electrocardiogram ( n = 4019; North America, 11%; Europe/ Australia/ Israel, 36%; South America, 26%; Asia, 4%; Africa, 23%; median age 36 years; 26% female). Results About 58.3% ( n = 2344) of the participants had at least one CVD risk factor and 18.9% ( n = 761) had two or more. The most common CVD risk factors were current smoking (32%), hypertension (19.3%) and obesity (16.5%). There were significant differences in the prevalence of CVD risk factors among geographical regions. The prevalence of at least one risk factor across regions was as follows: North America, 70.0%; Europe/ Australia/ Israel, 65.1%; South America, 49.4%; Asia, 37.0%; Africa, 55.8% ( P-value < 0.001). Significant regional differences were also observed when risk factors were used as part of the Framingham and Data Collection on Adverse events of Anti- HIV Drugs ( D: A: D) risk scores or used to define a favourable risk profile. Conclusions CVD risk factors are common among START participants, and their distribution varies by geographical region. Better understanding of how and why CVD risk factors develop in people with HIV infection and their geographical distributions could shed light on appropriate strategies for CVD prevention and may inform the interpretation of the results of START, as CVD is expected to be a major fraction of the primary endpoints observed. [ABSTRACT FROM AUTHOR]

Objectives Efforts are needed to improve informed consent of participants in research. The Strategic Timing of AntiRetroviral Therapy ( START) study provides a unique opportunity to study the effect of length and complexity of informed consent documents on understanding and satisfaction among geographically diverse participants. Methods Interested START sites were randomized to use either the standard consent form or the concise consent form for all of the site's participants. Results A total of 4473 HIV-positive participants at 154 sites world-wide took part in the Informed Consent Substudy, with consent given in 11 primary languages. Most sites sent written information to potential participants in advance of clinic visits, usually including the consent form. At about half the sites, staff reported spending less than an hour per participant in the consent process. The vast majority of sites assessed participant understanding using informal nonspecific questions or clinical judgment. Conclusions These data reflect the interest of START research staff in evaluating the consent process and improving informed consent. The START Informed Consent Substudy is by far the largest study of informed consent intervention ever conducted. Its results have the potential to impact how consent forms are written around the world. [ABSTRACT FROM AUTHOR]

Objectives The aim of this report is to describe the challenges, successes and patterns of enrolment in the Strategic Timing of AntiRetroviral Treatment ( START) study. Methods START is a collaboration of many partners with central coordination provided by the protocol team, the statistical and data management centre ( SDMC), the International Network for Strategic Initiatives in Global HIV Trials ( INSIGHT) network leadership, international coordinating centres and site coordinating centres. The SDMC prepared reports on study accrual, baseline characteristics and site performance that allowed monitoring of enrolment and data quality and helped to ensure the successful enrolment of this large international trial. We describe the pattern of enrolment and challenges faced during the enrolment period of the trial. Results An initial pilot phase began in April 2009 and established feasibility of accrual at 101 sites. In August 2010, funding approval for an expanded definitive phase led to the successful accrual of 4688 participants from 215 sites in 35 countries by December 2013. Challenges to accrual included regulatory delays (e.g. national/local ethics approval and drug importation approval) and logistical obstacles (e.g. execution of contracts with pharmaceutical companies, setting up of a central drug repository and translation of participant materials). The personal engagement of investigators, strong central study coordination, and frequent and transparent communication with site investigators, community members and participants were key contributing factors to this success. Conclusions Accrual into START was completed in a timely fashion despite multiple challenges. This success was attributable to the efforts of site investigators committed to maintaining study equipoise, transparent and responsive study coordination, and community involvement in problem-solving. [ABSTRACT FROM AUTHOR]

Objectives HIV-1 transmitted drug resistance ( TDR) in treatment-naïve individuals is a well-described phenomenon. Baseline genotypic resistance testing is considered standard of care in most developed areas of the world. The aim of this analysis was to characterize HIV-1 TDR and the use of resistance testing in START trial participants. Methods In the Strategic Timing of Anti Retroviral Treatment ( START) trial, baseline genotypic resistance testing results were collected at study entry and analysed centrally to determine the prevalence of TDR in the study population. Resistance was based on a modified 2009 World Health Organization definition to reflect newer resistance mutations. Results Baseline resistance testing was available in 1946 study participants. Higher rates of testing occurred in Europe (86.7%), the USA (81.3%) and Australia (89.9%) as compared with Asia (22.2%), South America (1.8%) and Africa (0.1%). The overall prevalence of TDR was 10.1%, more commonly to nonnucleoside reverse transcriptase inhibitors (4.5%) and nucleoside reverse transcriptase inhibitors (4%) compared with protease inhibitors (2.8%). The most frequent TDR mutations observed were M41L, D67 N/ G/ E, T215 F/ Y/ I/ S/ C/ D/ E/ V/ N, 219 Q/ E/ N/ R, K103 N/ S, and G190 A/ S/ E in reverse transcriptase, and M46 I/L and L90 M in protease. By country, the prevalence of TDR was highest in Australia (17.5%), France (16.7%), the USA (12.6%) and Spain (12.6%). No participant characteristics were identified as predictors of the presence of TDR. Conclusions START participants enrolled in resource-rich areas of the world were more likely to have baseline resistance testing. In Europe, the USA and Australia, TDR prevalence rates varied by country. [ABSTRACT FROM AUTHOR]

Background South Africa is experiencing a dietary and lifestyle transition as well as increased rates of noncommunicable chronic diseases. Limited information is available on the diets of rural populations. The present study aimed to characterise the diets of men and women from rural Kwa Zulu- Natal ( KZN) and develop a quantitative food-frequency questionnaire ( QFFQ) specific for this population. Methods A cross-sectional study was carried out by collecting single 24-h dietary recalls from 81 adults and developing a QFFQ in Empangeni, KZN, South Africa. Results The diet of this population was limited in variety, high in plant-based foods (especially cereals and beans), and low in animal products, vegetables and fruits. Amaize meal staple ( Phutu) was consumed by over 80% of subjects and accounted for almost 45% of energy intake, as well as making an important contribution to fat and protein intake. Most of the protein consumed by the study population was plant-based protein, with almost 40% being obtained from the consumption of phutu and beans. A culturally appropriate QFFQ was developed that includes 71 food and drink items, of which 16 are composite dishes unique to this population. Conclusions Once validated, this QFFQ can be used to monitor diet-disease associations, evaluate nutritional interventions and investigate dietary changes in this population. [ABSTRACT FROM AUTHOR]

Background: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction.Methods: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma.Results: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001).Conclusions: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.). [ABSTRACT FROM AUTHOR]