An Updated Economic Assessment of Moxidectin Treatment Strategies for Onchocerciasis Elimination.

BACKGROUND: Concerns that annual mass administration of ivermectin, the predominant strategy for onchocerciasis control and elimination, may not lead to elimination of parasite transmission (EoT) in all endemic areas have increased interest in alternative treatment strategies. One such strategy is moxidectin. We performed an updated economic assessment of moxidectin- relative to ivermectin-based strategies. METHODS: We investigated annual and biannual community-directed treatment with ivermectin (aCDTI, bCDTI) and moxidectin (aCDTM, bCDTM) with minimal or enhanced coverage (65% or 80% of total population taking the drug, respectively) in intervention-naive areas with 30%, 50%, or 70% microfilarial baseline prevalence (representative of hypo-, meso-, and hyperendemic areas). We compared programmatic delivery costs for the number of treatments achieving 90% probability of EoT (EoT90), calculated with the individual-based stochastic transmission model EPIONCHO-IBM. We used the costs for 40 years of program delivery when EoT90 was not reached earlier. The delivery costs do not include drug costs. RESULTS: aCDTM and bCDTM achieved EoT90 with lower programmatic delivery costs than aCDTI with 1 exception: aCDTM with minimal coverage did not achieve EoT90 in hyperendemic areas within 40 years. With minimal coverage, bCDTI delivery costs as much or more than aCDTM and bCDTM. With enhanced coverage, programmatic delivery costs for aCDTM and bCDTM were lower than for aCDTI and bCDTI. CONCLUSIONS: Moxidectin-based strategies could accelerate progress toward EoT and reduce programmatic delivery costs compared with ivermectin-based strategies. The costs of moxidectin to national programs are needed to quantify whether delivery cost reductions will translate into overall program cost reduction.

Great Cause-Small Effect: Undeclared Genetically Engineered Orange Petunias Harbor an Inefficient Dihydroflavonol 4-Reductase.

A recall campaign for commercial, orange flowering petunia varieties in spring 2017 caused economic losses worldwide. The orange varieties were identified as undeclared genetically engineered (GE)-plants, harboring a maize dihydroflavonol 4-reductase (DFR, A1), which was used in former scientific transgenic breeding attempts to enable formation of orange pelargonidin derivatives from the precursor dihydrokaempferol (DHK) in petunia. How and when the A1 cDNA entered the commercial breeding process is unclear. We provide an in-depth analysis of three orange petunia varieties, released by breeders from three countries, with respect to their transgenic construct, transcriptomes, anthocyanin composition, and flavonoid metabolism at the level of selected enzymes and genes. The two possible sources of the A1 cDNA in the undeclared GE-petunia can be discriminated by PCR. A special version of the A1 gene, the A1 type 2 allele, is present, which includes, at the 3'-end, an additional 144 bp segment from the non-viral transposable Cin4-1 sequence, which does not add any functional advantage with respect to DFR activity. This unequivocally points at the first scientific GE-petunia from the 1980s as the A1 source, which is further underpinned e.g., by the presence of specific restriction sites, parts of the untranslated sequences, and the same arrangement of the building blocks of the transformation plasmid used. Surprisingly, however, the GE-petunia cannot be distinguished from native red and blue varieties by their ability to convert DHK in common in vitro enzyme assays, as DHK is an inadequate substrate for both the petunia and maize DFR. Recombinant maize DFR underpins the low DHK acceptance, and, thus, the strikingly limited suitability of the A1 protein for a transgenic approach for breeding pelargonidin-based flower color. The effect of single amino acid mutations on the substrate specificity of DFRs is demonstrated. Expression of the A1 gene is generally lower than the petunia DFR expression despite being under the control of the strong, constitutive p35S promoter. We show that a rare constellation in flavonoid metabolism-absence or strongly reduced activity of both flavonol synthase and B-ring hydroxylating enzymes-allows pelargonidin formation in the presence of DFRs with poor DHK acceptance.

Knowledge of different medical and dental professional groups in Switzerland about halitosis.

Although halitosis is a widespread condition, it is still seen as too personal or embarrassing to talk about. The cause of real halitosis can be intraoral or extraoral. In order to determine the level of knowledge of health care providers in Switzerland, a survey was conducted over a period of three years in which 150 family physicians, 150 ear, nose and throat specialists, 154 dentists and 151 dental hygienists were personally interviewed. The survey shows that only 46.7% of the dentists and only 47.0% of the dental hygienists are consulted by patients for their halitosis, whereas 58.0% of the family physicians and 50.7% of the ENT specialists reported treating 1-10 patients for halitosis per year, while 46.7% of the ENT doctors even reported treating 11-100 patients for halitosis per year. 81.5% of all interviewed doctors and dental hygienists were of the opinion that halitosis mainly originates intraorally. 76.0% of the dentists and 72.8% of the dental hygienists as well as 33.3% of the family physicians recommend periodontitis therapy as halitosis treatment. This proves that a large percentage of medical professionals thinks that marginal periodontitis is the most common cause of halitosis. This study also shows that patients seek first consultations with dentists and dental hygienists less often than with family physicians and ENT specialists, despite the fact that the cause of halitosis is primarily intraoral.

Tyrosine-based signal mediates LRP6 receptor endocytosis and desensitization of Wnt/ß-catenin pathway signaling.

Wnt/ß-catenin signaling orchestrates a number of critical events including cell growth, differentiation, and cell survival during development. Misregulation of this pathway leads to various human diseases, specifically cancers. Endocytosis and phosphorylation of the LDL receptor-related protein 6 (LRP6), an essential co-receptor for Wnt/ß-catenin signaling, play a vital role in mediating Wnt/ß-catenin signal transduction. However, its regulatory mechanism is not fully understood. In this study, we define the mechanisms by which LRP6 endocytic trafficking regulates Wnt/ß-catenin signaling activation. We show that LRP6 mutant with defective tyrosine-based signal in its cytoplasmic tail has an increased cell surface distribution and decreased endocytosis rate. These changes in LRP6 endocytosis coincide with an increased distribution to caveolae, increased phosphorylation, and enhanced Wnt/ß-catenin signaling. We further demonstrate that treatment of Wnt3a ligands or blocking the clathrin-mediated endocytosis of LRP6 leads to a redistribution of wild-type receptor to lipid rafts. The LRP6 tyrosine mutant also exhibited an increase in signaling activation in response to Wnt3a stimulation when compared with wild-type LRP6, and this activation is suppressed when caveolae-mediated endocytosis is blocked. Our results reveal molecular mechanisms by which LRP6 endocytosis routes regulate its phosphorylation and the strength of Wnt/ß-catenin signaling, and have implications on how this pathway can be modulated in human diseases.

Knowledge of halitosis among dentists and dental hygienists.

Bad breath is a widespread condition that has been increasingly discussed among professionals and in the mass media in the last few years. In nine of ten cases, halitosis originates intraorally; hence it has become an important topic of study in the education and training of dentists and dental hygienists. However, the de facto knowledge of professionals has never been examined until today. 750 dentists and dental hygienists from Switzerland, Germany, and France were personally interviewed. Their knowledge of halitosis was assessed using a specifically designed questionnaire. In general, considerable differences were ascertained between the German-speaking countries and France, dentists and dental hygienists, and women and men. 27.5% of the French participants believed that the underlying cause of halitosis has a non-oral nature, whereas only 8% of the Swiss and German participants believed so (p ⟨ 0.001). In contrast to dental hygienists, dentists more often considered gastrointestinal factors as a cause of halitosis (p ⟨ 0.001). Dental hygienists from Switzerland and Germany more frequently reported the use of tongue scrapers as a therapeutic method (97% and 97.3%) than did dentists of the same countries (87.3% and 89.3%). Among the French participants, only 52% mentioned the use of tongue scrapers to treat halitosis. 2.7% of French dental professionals had participated in a continuing education course about halitosis, which is much lower than the rate of attendance in Switzerland and Germany (46%). Additionally, interdisciplinary discrepancies were observed, as 65.3% of the dental hygienists frequented advanced training courses, which was twice as much as dentists. Therefore, there are clear differences between dentists in France and their colleagues from the German-speaking countries, but also between dental hygienists and dentists. Dental hygienists from Switzerland and Germany appear to be far ahead in terms of halitosis knowledge.

Development of healthy eating and physical activity quality standards for out-of-school time programs.

BACKGROUND: Out-of-school time (OST) programs serve over 8 million children per year and have ample opportunity to promote health through menu and physical activity choices. Until recently, however, the field has lacked a comprehensive set of operationalizable standards for healthy eating and physical activity. The National AfterSchool Association adopted voluntary healthy eating and physical activity quality standards (HEPAQS) in April, 2011. METHODS: We describe the development of HEPAQS. This work reflects a social ecological model for changing children's eating and activity behaviors through program-level interventions. The standards were developed using a national, mixed-methods needs assessment, review of existing standards and expert recommendations, and a participatory process of discussion, review, and consensus engaging 19 influential service and policy organizations and agencies in the Healthy Out-of-School Time (HOST) coalition, which we convened in 2009. RESULTS: The HOST coalition approved a final version of the HEPAQS in January, 2011. The 11 standards address content, curriculum selection, staff training, program support, and environmental support for healthy eating and physical activity. In April, 2011, the HEPAQS were adopted by the National AfterSchool Association, and have subsequently been widely disseminated. Extensive adoption and implementation efforts are underway. CONCLUSIONS: The availability of a comprehensive set of standards for healthy eating and physical activity in OST provides practical information to help community-based youth-serving organizations participate in obesity and chronic disease prevention. A working awareness of their content will be useful to scientists undertaking health promotion studies in the out-of-school time setting.

Effect of an after-school intervention on increases in children's physical activity.

PURPOSE: Evaluate the effect of an after-school intervention on physical activity program changes and individual behaviors among children. METHODS: A quasi-experimental evaluation of a YMCA-driven environmental change intervention with 16 intervention and 16 control sites in four metropolitan areas in the United States. Intervention sites participated in learning collaboratives designed to promote physical activity and nutrition through environmental change, educational activities, and parent engagement. Behavioral foci included increasing overall physical activity levels as well as combined moderate and vigorous physical activity and vigorous physical activity. Outcomes were assessed longitudinally using preintervention and follow-up surveys of program implementation and accelerometer measures of physical activity. ActiGraph accelerometer data were collected from a sample of 212 children, ages 5-11 yr, attending the programs. On average, 3 d of data were gathered per child. Reliability of the accelerometer counts averaged 0.78. Multivariate regression models were used to control for potential confounding variables and to account for clustering of observations. RESULTS: Data indicate greater physical activity increases in children in intervention versus control sites after modest intervention implementation. Controlling for baseline covariates, children in intervention sites showed greater increases in average physical activity level than in control sites (76 counts per minute, P = 0.037, 95% confidence interval (CI) = 8.1-144) and more minutes of moderate and vigorous physical activity (10.5 min·d(-1), P = 0.017, 95% CI = 1.5-18.6), minutes of moderate physical activity (5.6 min·d(-1), P = 0.020, 95% CI = 0.99-10.2), and minutes of vigorous physical activity (5.1 min·d(-1), P = 0.051, 95% CI = 0.21-9.93). CONCLUSIONS: Results indicate significant increases in daily physical activity among children in intervention versus control sites. This study documents the effectiveness of an environmental change approach in an applied setting.

Disseminating health promotion practices in after-school programs through YMCA learning collaboratives.

PURPOSE: We describe the perceived usefulness of a learning collaborative for translating obesity prevention science into practice at YMCA after-school programs. APPROACH: We conducted mixed-methods research to identify beneficial aspects of the collaborative and to assess perceived effect of the collaborative on ability to meet goals. SETTING: Sixty-one YMCA after-school programs serving roughly 2500 children in 21 states. PARTICIPANTS: After-school program staff attending learning sessions for the collaborative. INTERVENTION: YMCA learning collaboratives comprise a structured organizational change process delivered during 9 to 12 months that aim to empower staff to find local methods for achieving specific program outcomes related to diet and physical activity. RESEARCH METHOD: Eight focus groups conducted during the collaboratives assessed their usefulness. A post hoc Web-based follow-up survey (39 respondents; response rate, 40.6%) assessed final perceived effect. RESULTS: Qualitative and quantitative data were highly positive about the usefulness of the collaborative. The collaboratives' duration, peer learning, multilevel staff involvement, focus on creating a supportive organization, and regular coaching support enabled many respondents to make program and policy changes consistent with project goals. There was consensus that executive-level commitment to the work was critical. CONCLUSION: Learning collaboratives are a promising tool for embedding health promotion practices in existing after-school programs through a structured organizational change process.

Impact of an organizational intervention designed to improve snack and beverage quality in YMCA after-school programs.

OBJECTIVES: We evaluated the quality of snacks and beverages served at YMCA after-school programs before and after the programs' participation in a YMCA Learning Collaborative. METHODS: We collected data on the types and brands of snacks and beverages (including fresh fruits and vegetables, whole grains, foods with trans fats, water, and sugar-sweetened beverages) served daily during 3 different time periods spanning 14 months in total, and the components of the healthy eating standards. We compared snack and beverage quality before and after the intervention. RESULTS: Weekly servings of fresh fruits and vegetables (1.3 vs 3.9; P = .02) and weekly servings of fruits and vegetables as a whole (1.9 vs 5.2; P = .009) increased from baseline to postintervention; weekly servings of desserts (1.3 vs 0.5; P = .049), foods with added sugars (3.9 vs 2.4; P = .03), and foods containing trans fats (2.6 vs 0.7; P = .01) decreased. After the intervention, all YMCAs offered water daily, and none served sugar-sweetened beverages. The percentage of calories from fruits and vegetables significantly increased after the intervention, whereas the percentage of calories from foods containing trans fats and added sugars decreased. CONCLUSIONS: A learning collaborative can disseminate healthy eating standards among participating organizations and facilitate improvements in the quality of after-school snacks and beverages.