Genetic Covariation Between the Vertically Transmitted Endophyte Epichloë canadensis and Its Host Canada Wildrye.

Symbiotic mutualisms are thought to be stabilized by correlations between the interacting genotypes which may be strengthened via vertical transmission and/or reduced genetic variability within each species. Vertical transmission, however, may weaken interactions over time as the endosymbionts would acquire mutations that could not be purged. Additionally, temporal variation in a conditional mutualism could create genetic variation and increased variation in the interaction outcome. In this study, we assessed genetic variation in both members of a symbiosis, the endosymbiotic fungal endophyte Epichloë canadensis and its grass host Canada wildrye (Elymus canadensis). Both species exhibited comparable levels of diversity, mostly within populations rather than between. There were significant differences between populations, although not in the same pattern for the two species, and the differences were not correlated with geographic distance for either species. Interindividual genetic distance matrices for the two species were significantly correlated, although all combinations of discriminant analysis of principle components (DAPC) defined multilocus genotype groups were found suggesting that strict genotype matching is not necessary. Variation in interaction outcome is common in grass/endophyte interactions, and our results suggest that the accumulation of mutations overtime combined with temporal variation in selection pressures increasing genetic variation in the symbiosis may be the cause.

How often does the preoperative plan for freehand pedicle screw placement match the actual surgical execution in adolescent idiopathic scoliosis?

PURPOSE: To provide a baseline for comparison with future advancements, this study determined the accuracy of preoperative planning of pedicle screw placement using standard radiographs for posterior fusion (PSF) for adolescent idiopathic scoliosis (AIS). METHODS: Ninety-five patients with AIS planned for PSF were prospectively enrolled. Preoperative planning was based upon standard upright posteroanterior and lateral radiographs. The planned number of screws to be placed at each level was recorded. Intraoperatively, all screws were placed by freehand technique. The number of successfully placed screws and the reasons for abandoning screw placement were documented. RESULTS: There were a total of 1783 pedicle screws planned preoperatively. The average planned implant density was 2.0 implants/vertebra. A total of 1723 (96.6%) of the planned screws were placed successfully. Fourteen (0.8%) screws were abandoned after attempted placement (range 0-2 screws/case). Of 241 screws planned in pedicles noted to be "hypoplastic," 13 resulted in the use of a hook or no instrumentation. The placement was not attempted for 49 (range 0-7/case) planned screws due to intraoperative decision-making and a sense that the curve was flexible enough not to require every screw. Three cases (3.2%) required instrumentation of an additional level. CONCLUSIONS: Standard spine radiographs allow for accurate preoperative planning for freehand pedicle screw placement in AIS. Ninety-seven percent of planned screws were placed successfully. The primary reason for deviation from the preoperative plan was intraoperative surgeon decision-making rather than difficulty with screw placement. This study will serve as a baseline when considering the utilization of navigation in PSF for AIS.

Omega-3 fatty acid supplementation in pregnancy-baseline omega-3 status and early preterm birth: exploratory analysis of a randomised controlled trial.

OBJECTIVE: To identify a polyunsaturated fatty acid (PUFA) biomarker able to detect which women with singleton pregnancies are most likely to benefit from omega-3 supplementation to reduce their risk of early preterm birth. DESIGN: Exploratory analysis of a randomised controlled trial. SETTING: Six Australian hospitals. POPULATION: Women with a singleton pregnancy enrolled in the ORIP trial. METHODS: Using maternal capillary whole blood collected ~14 weeks' gestation, the fatty acids in total blood lipids were quantified using gas chromatography. Interaction tests examined whether baseline PUFA status modified the effect of omega-3 supplementation on birth outcomes. MAIN OUTCOME MEASURE: Early preterm birth (<34 weeks' gestation). RESULTS: A low total omega-3 PUFA status in early pregnancy was associated with a higher risk of early preterm birth. Among women with a total omega-3 status ≤4.1% of total fatty acids, omega-3 supplementation substantially reduced the risk of early preterm birth compared with control (0.73 versus 3.16%; relative risk = 0.23, 95% confidence interval [CI] 0.07-0.79). Conversely, women with higher total omega-3 status in early pregnancy were at lower risk of early preterm birth. Supplementing women with a baseline status above 4.9% increased early preterm birth (2.20 versus 0.97%; relative risk = 2.27, 95% CI 1.13-4.58). CONCLUSIONS: Women with singleton pregnancies and low total omega-3 PUFA status early in pregnancy have an increased risk of early preterm birth and are most likely to benefit from omega-3 supplementation to reduce this risk. Women with higher total omega-3 status are at lower risk and additional omega-3 supplementation may increase their risk. TWEETABLE ABSTRACT: Low total omega-3 fat status helps identify which women benefit from extra omega-3 to reduce early prematurity.

Beer spoilage and low pH tolerance is linked to manganese homeostasis in selected Lactobacillus brevis strains.

AIMS: Beer is a harsh medium for bacteria to survive, however, lactic acid bacteria including Lactobacillus brevis have evolved the ability to grow in beer. Here, the influence of environmental factors such as low pH, ethanol or hop content was assessed. METHODS AND RESULTS: A transcriptomic analysis of two Lact. brevis beer-spoiling strains was performed comparing growth in nutritive media with or without the imposition of a stressor related to the beer environment. This allowed the identification of a manganese transporter encoding gene that contributes to low pH tolerance. CONCLUSIONS: We report on the importance of a manganese transporter associated with pH tolerance and beer spoilage in Lact. brevis. The importance of manganese for Lact. brevis growth in a low pH environment was highlighted. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacterial spoilage of beer may result in product withdrawal with concomitant economic losses for the brewing industry. A limited number of genes involved in beer spoilage have been identified but none of them are universal. It is clear that other molecular players are involved in beer spoilage. The study highlights the complexity of the genetic requirements to facilitate beer spoilage and the role of multiple key players in this process.

Barriers and enablers in the implementation of a standardised process for nutrition care: findings from a multinational survey of dietetic professionals in 10 countries.

BACKGROUND: To explore the barriers and enablers experienced by nutrition and dietetic professionals in the implementation of the standardised Nutrition Care Process (NCP) across 10 different countries. NCP related beliefs, motivations and values were investigated and compared. METHODS: A validated online survey was disseminated to nutrition and dietetics professionals in 10 countries in the local language during 2017. Cross-sectional associations and differences between countries were explored for level of implementation, barriers/enablers and attitudes/motivation among the respondents. RESULTS: Higher NCP implementation was associated with greater occurrence of enabling aspects, as well as fewer occurrences of barriers. The most common enabler was 'recommendation by the national dietetic association' (69%) and the most common barrier was 'lack of time' (39%). A longer experience of NCP use was associated with a more positive attitude towards all NCP aspects. Differences between countries were identified, regarding both the occurrence of barriers/enablers and attitudes/motivations. CONCLUSIONS: Implementation efforts need to be tailored to country-specific contexts when implementing a new standard of care framework among nutrition and dietetic professionals. Additional research is needed to further assess the management and workplace strategies to support the development of nutrition and dietetics professionals in multidisciplinary healthcare organisations.

Short communication: Characterizing ovine serum stress biomarkers during endotoxemia.

Breeding stress-resilient livestock is a potential strategy to help mitigate the negative effect of environmental and pathogenic stressors. The hypothalamic-pituitary-adrenal axis and immune system are activated during stress events and release mediators into the circulation that help restore physiological homeostasis. The purpose of this study was to assess a comprehensive set of circulatory mediators released in response to an acute immune stress challenge to identify candidate biomarkers that can be used for the selection of stress-resilient animals. Fifteen female lambs were stress challenged with an intravenous bolus of lipopolysaccharide (LPS; 400 ng/kg), and blood was collected from the jugular vein at 0, 2, 4, and 6 h after LPS challenge to identify and monitor candidate stress biomarkers; temperature was also recorded over time. Biomarker responses were evaluated with a repeated-measures model to compare time points with baseline values. As expected, all sheep had a monophasic febrile response to LPS challenge, and cortisol increased and returned to baseline by 6 h. The cytokines tumor necrosis factor-α, IL-6, IFN-γ (proinflammatory), and IL-10 (anti-inflammatory) increased, but only tumor necrosis factor-α returned to baseline during the monitoring period. The cytokines IL-1α, IL-1ß, IL-17α (proinflammatory), and IL-4 (anti-inflammatory) did not respond to LPS challenge. All chemokines (CCL2, CCL3, CCL4, CXCL10, and IL-8) responded to LPS challenge; however, only CCL2, CCL3, CCL4, and CXCL10 increased over time, and only CCL3, CCL4, and CXCL10 returned to baseline during the monitoring period. MicroRNA (miR-145, miR-233, and miR-1246) also increased and remained elevated during the study. In summary, the LPS challenge induced a strong stress response in Rideau-Dorset sheep that could be monitored with a distinct profile of circulatory biomarkers.

Development of an Insulin-Prescribing Chart for Paediatric Diabetes

Aim Our aim was to design a new insulin prescribing tool in compliance with the Irish Medicines Safety Network recommendations. Methods In 2015, we undertook a review of the existing paediatric subcutaneous insulin-prescribing sheet introduced to Cork University Hospital in 2013. This involved a retrospective analysis of 15 consecutive in-patient insulin prescribing charts and a questionnaire distributed to health professionals. Following this a new insulin prescribing chart was designed and implemented in 2016 and a re-audit was performed in 2017. Results The 2017 re-audit demonstrated that the new insulin chart was viewed as easier (95% of previous users n=18) and safer (n=16) to use. There was less confusion (2017: 28%, n=11/39 vs 2015: 50%, n=17/34 2015) and the ALERT system helped staff standardise hypo/hyperglycaemia management (71%, n=28). Conclusion The new paediatric insulin prescribing chart has improved safety and ease of prescribing insulin. The colour coded quasi graph and ALERT system has made it easier to appreciate capillary blood glucose trends and manage them safely.

Selective thoracic fusion of a left decompensated main thoracic curve: proceed with caution?

PURPOSE: Previous research has shown that with certain idiopathic scoliosis curve types, performing a selective thoracic fusion (STF) is associated with an increased risk of coronal decompensation post-operatively. The purpose of the current study was to determine the influence of curve correction and fusion level on post-operative balance in STF for adolescent idiopathic scoliosis patients with pre-operative coronal decompensation. METHODS: A multicenter database was queried for subjects with right Lenke 1-4C curves, pre-operative left coronal imbalance, and 2-year follow-up who underwent STF (caudal fusion level of L1 or proximal). Rates of decompensation were compared between groups with different levels of fusion. Thoracic and lumbar curve correction as well as Scoliosis Research Society-22 outcome scores were compared between groups that were post-operatively balanced or persistently decompensated. RESULTS: 121 patients were identified with average thoracic and lumbar curves of 53° and 41°. Mean pre- and post-operative decompensations were 2.4 ± 1.0 and 1.8 ± 1.1 cm, respectively. Eighteen patients were fused short, 62 to, and 41 were fused past the stable vertebra. Ten patients were fused short, 32 to, and 78 were fused past the neutral vertebra. Incidence of post-operative decompensation was 41%. No differences in post-operative decompensation relative to the stable or neutral vertebra were noted (p = 0.66, p = 0.74). Post-operatively, those patients who were balanced had similar thoracic curve correction (58%) to those decompensated (54%, p = 0.11); however, patients balanced post-operatively had greater SLCC (45 vs 40%, p = 0.04). No differences in SRS-22 outcome scores were noted between groups (p > 0.05). CONCLUSIONS: There was a high rate of post-operative decompensation in patients with pre-operative coronal decompensation undergoing STF. Fusion to or past the stable or neutral vertebra did not affect the risk of persistent decompensation. Attempts to improve SLCC could reduce post-operative decompensation.

Population genetic structure and comparative diversity of smallmouth bass Micropterus dolomieu: congruent patterns from two genomes.

Genetic diversity and divergence patterns of smallmouth bass Micropterus dolomieu spawning groups are analysed across its northern native range with mtDNA cytochrome b gene sequences and eight unlinked nuclear DNA microsatellite loci. Results reveal high levels of genetic variability and significant differences in allelic representation among populations (mtDNA: mean ± s.e., HD = 0·50 ± 0·06, mean ± s.e., θST = 0·41 ± 0·02 and microsatellites: mean ± s.e. HO = 0·46 ± 0·03, mean ± s.e. θST = 0·25 ± 0·01). The distributions of 28 variant mtDNA haplotypes, which differ by an average of 3·94 nucleotides (range = 1-8), denote divergent representation among geographic areas. Microsatellite data support nine primary population groups, whose high self-assignment probabilities likewise display marked divergence. Genetic patterns demonstrate: (1) high genetic diversity in both genomes, (2) significant divergence among populations, probably resulting from natal site homing and low lifetime migration, (3) support for three post-glacial refugia that variously contributed to the current northern populations, which remain evident today despite waterway connectivity and (4) a weak yet significant genetic isolation by geographic distance pattern, indicating that other processes affect the differences among populations, such as territoriality and site fidelity.

Diffuse optical spectroscopic imaging of subcutaneous adipose tissue metabolic changes during weight loss.

BACKGROUND: Changes in subcutaneous adipose tissue (AT) structure and metabolism have been shown to correlate with the development of obesity and related metabolic disorders. Measurements of AT physiology could provide new insight into metabolic disease progression and response to therapy. An emerging functional imaging technology, diffuse optical spectroscopic imaging (DOSI), was used to obtain quantitative measures of near infrared (NIR) AT optical and physiological properties. METHODS: Ten overweight or obese adults were assessed during 3 months on calorie-restricted diets. DOSI-derived tissue concentrations of hemoglobin, water and lipid and the wavelength-dependent scattering amplitude (A) and slope (b) obtained from 30 abdominal locations and three time points (T0, T6, T12) were calculated and analyzed using linear mixed-effects models and were also used to form 3D surface images. RESULTS: Subjects lost a mean of 11.7±3.4% of starting weight, while significant changes in A (+0.23±0.04 mm(-1), adj. P<0.001),b (-0.17±0.04, adj. P<0.001), tissue water fraction (+7.2±1.1%, adj. P<0.001) and deoxyhemoglobin (1.1±0.3 µM, adj. P<0.001) were observed using mixed-effect model analysis. DISCUSSION: Optical scattering signals reveal alterations in tissue structure that possibly correlate with reductions in adipose cell volume, while water and hemoglobin dynamics suggest improved AT perfusion and oxygen extraction. These results suggest that DOSI measurements of NIR optical and physiological properties could be used to enhance understanding of the role of AT in metabolic disorders and provide new strategies for diagnostic monitoring of obesity and weight loss.

Hepatitis C Seroprevalence Among HIV-Infected Childbearing Women in New York State in 2006.

OBJECTIVE: To identify factors associated with maternal hepatitis C virus (HCV) seroprevalence and transmission of HCV as identified by qualitative HCV ribonucleic acid (RNA) in the infants of human immunodeficiency virus (HIV) infected women delivering in New York State (NYS) in 2006. STUDY DESIGN: In this retrospective cohort study of HIV-exposed infants born in NYS, leftover infant plasma from HIV diagnostic testing was de-identified and tested for HCV. If HCV antibodies were detected, a second specimen collected when the infant was >2 months old was tested for HCV qualitative RNA. Multivariate logistic regression was used to identify factors associated with HCV seropositivity. RESULTS: In a final sample of 553 live birth events with perinatal HIV exposure, 21 (3.8 %) of tested infant specimens had HCV antibodies indicative of maternal HCV seropositivity. Maternal age at delivery of >35 years, Hispanic ethnicity, white race and injection drug use (IDU) were significantly associated with HCV seropositivity in multivariate analysis. No cases of HCV vertical transmission were identified among HCV exposed infant specimens. CONCLUSIONS: This statewide population-based study of HIV-infected childbearing women shows HCV seroprevalence of 3.8 %. Maternal age of >35 years and IDU are the strongest predictors of HCV seropositivity. Although no viral transmission was documented, more comprehensive longitudinal testing would be required to conclude that HCV transmission did not occur.

Evolutionary etiology of high-grade astrocytomas.

Glioblastoma (GBM), the most common brain malignancy, remains fatal with no effective treatment. Analyses of common aberrations in GBM suggest major regulatory pathways associated with disease etiology. However, 90% of GBMs are diagnosed at an advanced stage (primary GBMs), providing no access to early disease stages for assessing disease progression events. As such, both understanding of disease mechanisms and the development of biomarkers and therapeutics for effective disease management are limited. Here, we describe an adult-inducible astrocyte-specific system in genetically engineered mice that queries causation in disease evolution of regulatory networks perturbed in human GBM. Events yielding disease, both engineered and spontaneous, indicate ordered grade-specific perturbations that yield high-grade astrocytomas (anaplastic astrocytomas and GBMs). Impaired retinoblastoma protein RB tumor suppression yields grade II histopathology. Additional activation of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) network drives progression to grade III disease, and further inactivation of phosphatase and tensin homolog (PTEN) yields GBM. Spontaneous missense mutation of tumor suppressor Trp53 arises subsequent to KRAS activation, but before grade III progression. The stochastic appearance of mutations identical to those observed in humans, particularly the same spectrum of p53 amino acid changes, supports the validity of engineered lesions and the ensuing interpretations of etiology. Absence of isocitrate dehydrogenase 1 (IDH1) mutation, asymptomatic low grade disease, and rapid emergence of GBM combined with a mesenchymal transcriptome signature reflect characteristics of primary GBM and provide insight into causal relationships.

Efficacy of low concentrations of sodium hypochlorite and low-powered Er,Cr:YSGG laser activated irrigation against an Enterococcus faecalis biofilm.

AIM: To establish the antibacterial efficacy of low concentrations of sodium hypochlorite with and without Er,Cr:YSGG laser activation on Enterococcus faecalis biofilms in extracted teeth. METHODOLOGY: The root canals of 96 decoronated single-rooted extracted human teeth were prepared to a size 40, 0.06 taper 1 mm beyond the apex. They were mounted within a flow cell, which was sterilized before pumping a nutrient media through the root canals. The flow cell was inoculated with E. faecalis (ATCC 700802) and cultivated for 4 weeks. The root-ends were sealed, and the roots were then subjected to one of six treatment groups: group 1: syringe irrigation (SI) with saline (control) using a 27 -gauge Monoject needle 1 mm from the apex for 2 min; group 2: as for group 1 but with 1% NaOCl; group 3: as for group 1 but with 4% NaOCl; group 4: 0.5% NaOCl irrigation for 15 s followed by laser-activated irrigation (LAI) with four 15-s cycles replenishing the irrigant between cycles; group 5: as for group 4 but with 1% NaOCl as the irrigant; group 6: as for group 4 but with 4% NaOCl as the irrigant. Following treatment, teeth were crushed and viable bacteria were quantitated by serial dilution and plating. The colony-forming unit values were compared between groups using one-way anova and Tukey-adjusted post hoc tests. A two-tailed P value of <0.05 was considered statistically significant. RESULTS: The mean number of cells recovered from the 1% NaOCl SI group was significantly higher than that from the 4% NaOCl LAI group (P = 0.02). CONCLUSION: Within the limitations of this laboratory study, low-powered (0.5 W) Er,Cr:YSGG laser activation did not improve the antibacterial effect of low concentrations of sodium hypochlorite.

Improved Measurement of the π→eν Branching Ratio.

A new measurement of the branching ratio R_{e/µ}=Γ(π^{+}→e^{+}ν+π^{+}→e^{+}νγ)/Γ(π^{+}→µ^{+}ν+π^{+}→µ^{+}νγ) resulted in R_{e/µ}^{exp}=[1.2344±0.0023(stat)±0.0019(syst)]×10^{-4}. This is in agreement with the standard model prediction and improves the test of electron-muon universality to the level of 0.1%.

Radiation exposure to comforters and carers during paediatric molecular radiotherapy.

BACKGROUND: To show whether the incidental radiation exposure received by comforters and carers of children undergoing molecular radiotherapy was kept as low as reasonably achievable and was within English national dose constraints. PROCEDURE: The radiation exposure of adult comforters and carers was routinely monitored with a whole body personal dose meter while the child was in hospital. Data were collected on iodine-131 meta-iodobenzylguanidine (131 I-mIBG), lutetium-177 DOTATATE (177 Lu-DOTATATE), and iodine-131 sodium iodide (131 I-NaI) treatments. RESULTS: Data were available for 50 treatments with high-administered activity double-infusion 131 I-mIBG and 12 single administrations; 15 177 Lu-DOTATATE treatments and 28 131 I-NaI administrations. The median age was 7 years (1-18). The median administered activity of: 131 I-mIBG was 16.2 GBq (6.8-59 GBq) for double infusion patients and 8.1 GBq (5.26-16.25 GBq) for single administrations; 177 Lu-DOTATATE was 7.2 GBq (2.5-7.5 GBq); and 131 I-NaI was 3 GBq for thyroid remnant ablation and 5.5 GBq for cancer therapy. The median number of comforters and carers for all administrations was 2 (range 1-9). The median exposure values for comforters and carers for high-administered activity 131 I-mIBG administrations was 302 µSv (0-5282 µSv); for single fraction 131 I-mIBG 163 µSv (3-3104 µSv); 177 Lu-DOTATATE 6 µSv (1-79 µSv); and 131 I-NaI 37 µSv (0-274 µSv). Only one of the comforters and carers exceeded the dose constraint of 5 mSv. CONCLUSIONS: Doses to comforters and carers were in all but one case within the dose constraint nationally recommended by the Health Protection Agency, now part of Public Health England. New evidence is presented which show that comforter and carer radiation exposure levels from paediatric molecular radiotherapy in routine clinical practice are acceptably low. Pediatr Blood Cancer 2015;62:235-239. © 2014 Wiley Periodicals, Inc.

Dairy product consumption, dietary nutrient and energy density and associations with obesity in Australian adolescents.

BACKGROUND: Dairy intake is likely to influence dietary energy density (ED) and nutrient density (ND), which are factors representing aspects of dietary quality. Although evidence suggests dairy intake is unlikely to contribute to obesity, intake tends to decrease over adolescence, potentially as a result of concerns around weight gain. We examined associations between dairy intake, ED and ND, and investigated relationships with obesity in adolescents. METHODS: The present study comprised a cross-sectional study of 1613 14-year-olds in the Western Australian Pregnancy Cohort (Raine) Study. Adolescents completed a 212-item food frequency questionnaire. Nutrient Rich Food index 9.3 (NRF9.3) was used to estimate ND. Age-specific body mass index (BMI) and waist-height cut-offs were used to categorise obesity risk. RESULTS: Mean (SD) dairy intake was: 2.62 (1.51) servings daily; ED was 4.53 (0.83) (food and beverage) and 6.28 (1.33) (food only); ND was 373 (109). Dairy intake was inversely associated with ED and positively associated with ND. The odds of being overweight (as assessed by BMI) increased by 1.24 (95% confidence interval = 1.09-1.42) with each 100-point increase in ND, after adjustment for potential confounders and energy intake. ED measures and dairy intake were inversely associated with obesity after adjustment for confounders; associations became nonsignificant after energy adjustment. CONCLUSIONS: The NRF9.3 was originally designed to assess foods, not diets. Further research in other cohorts to determine whether similar findings exist, or investigations into alternate measures of dietary ND, may prove useful. Our findings may be the result of factors such as an excess consumption of refined but fortified foods. Although higher dairy intakes were associated with higher ND, intakes were not associated with higher obesity risk.

Are trajectories of self-regulation abilities from ages 2-3 to 6-7 associated with academic achievement in the early school years?

BACKGROUND: The aim of this study was to estimate the association between two key aspects of self-regulation, 'task attentiveness' and 'emotional regulation' assessed from ages 2-3 to 6-7 years, and academic achievement when children were aged 6-7 years. METHODS: Participants (n = 3410) were children in the Longitudinal Study of Australian Children. Parents rated children's task attentiveness and emotional regulation abilities when children were aged 2-3, 4-5 and 6-7. Academic achievement was assessed using the Academic Rating Scale completed by teachers. Linear regression models were used to estimate the association between developmental trajectories (i.e. rate of change per year) of task attentiveness and emotional regulation, and academic achievement at 6-7 years. RESULTS: Improvements in task attentiveness between 2-3 and 6-7 years, adjusted for baseline levels of task attentiveness, child and family confounders, and children's receptive vocabulary and non-verbal reasoning skills at age 6-7 were associated with greater teacher-rated literacy [B = 0.05, 95% confidence interval (CI) = 0.04-0.06] and maths achievement (B = 0.04, 95% CI = 0.03-0.06) at 6-7 years. Improvements in emotional regulation, adjusting for baseline levels and covariates, were also associated with better teacher-rated literacy (B = 0.02, 95% CI = 0.01-0.04) but not with maths achievement (B = 0.01, 95% CI = -0.01-0.02) at 6-7 years. For literacy, improvements in task attentiveness had a stronger association with achievement at 6-7 years than improvements in emotional regulation. CONCLUSIONS: Our study shows that improved trajectories of task attentiveness from ages 2-3 to 6-7 years are associated with improved literacy and maths achievement during the early school years. Trajectories of improving emotional regulation showed smaller effects on academic outcomes. Results suggest that interventions that improve task attentiveness when children are aged 2-3 to 6-7 years have the potential to improve literacy and maths achievement during the early school years.

Can Internet information on vertebroplasty be a reliable means of patient self-education?

BACKGROUND: Studies of the quality and accuracy of health and medical information available on the Internet have shown that many sources provide inadequate information. However, to our knowledge, there are no published studies analyzing the quality of information available online regarding vertebroplasty. Because this has been a high-volume procedure with highly debated efficacy, it is critical that patients receive complete, accurate, and well-balanced information before deciding a treatment course. Additionally, few studies have evaluated the merit of academic site authorship or site certification on information quality, but some studies have used measurements of quality that are based primarily on subjective criteria or information accuracy rather than information completeness. QUESTIONS/PURPOSES: The purposes of our study were (1) to evaluate and analyze the information on vertebroplasty available to the general public through the Internet; (2) to see if sites sponsored by academic institutions offered a higher quality of information; and (3) to determine whether quality of information varied according to site approval by a certification body. METHODS: Three search engines were used to identify 105 web sites (35 per engine) offering information regarding vertebroplasty. Sites were evaluated for authorship/sponsorship, content, and references cited. Information quality was rated as "excellent," "high," "moderate," "low," or "unacceptable." Sites also were evaluated for contact information to set up an appointment. Data were analyzed as a complete set, then compared between authorship types, and finally evaluated by certification status. Academic sites were compared with other authorship groups and certified sites were compared with noncertified sites using Student's t-test. RESULTS: Appropriate indications were referenced in 74% of sites, whereas only 45% discussed a contraindication to the procedure. Benefits were expressed by 100% of sites, but risks were outlined in only 53% (p < 0.001). Ninety-nine percent of sites provided step-by-step descriptions of the procedure, and 44% of sites also included images. Alternative treatments were mentioned by 51% of sites. Twenty-seven percent of sites referenced peer-reviewed literature, 41% offered experiential or noncited data based on American populations, and 7% offered analogous data from international populations. Thirty percent of sites provided contact information for patient appointment scheduling. Seven percent of sites were classified as excellent quality, 6% as high quality, 11% as moderate quality, 19% as poor quality, and 57% as unacceptable. Sixteen percent of sites were sponsored by academic institutions, 62% by private groups, 8% by biomedical device companies, and 14% were sponsored otherwise. Academic sites reported fewer risks of the procedure than private sites or other sites (p = 0.05 and p = 0.04), but reported more risks than industry sites (p = 0.007). Academic sites were more likely than sites classified as other to offer contact information for patient appointment scheduling (p = 0.004). Nine percent of sites evaluated were Health on the Net Foundation (HONCode) certified. No association with improved information quality was observed in these sites relative to noncertified sites (all p > 0.05). CONCLUSIONS: Internet information regarding vertebroplasty is not only inadequate for proper patient education, but also potentially misleading as sites are more likely to present benefits of the procedure than risks. Although academic sites might be expected to offer higher-quality information than private, industry, or other sites, our data would suggest that they do not. HONCode certification cannot be used reliably as a means of qualifying website information quality. Academic sites should be expected to set a high standard and alter their Internet presence with adequate information distribution. Certification bodies also should alter their standards to necessitate provision of complete information in addition to emphasizing accurate information. Treating physicians may want to counsel their patients regarding the limitations of information present on the Internet and the pitfalls of current certification systems. LEVEL OF EVIDENCE: Level IV, economic and decision analyses. See the Instructions for Authors for a complete description of levels of evidence.

Spatiotemporal modulation of growth factors directs the generation of multilineage mouse embryonic stem cell-derived mammary organoids.

Ectodermal appendages, such as the mammary gland (MG), are thought to have evolved from hair-associated apocrine glands to serve the function of milk secretion. Through the directed differentiation of mouse embryonic stem cells (mESCs), here, we report the generation of multilineage ESC-derived mammary organoids (MEMOs). We adapted the skin organoid model, inducing the dermal mesenchyme to transform into mammary-specific mesenchyme via the sequential activation of Bone Morphogenetic Protein 4 (BMP4) and Parathyroid Hormone-related Protein (PTHrP) and inhibition of hedgehog (HH) signaling. Using single-cell RNA sequencing, we identified gene expression profiles that demonstrate the presence of mammary-specific epithelial cells, fibroblasts, and adipocytes. MEMOs undergo ductal morphogenesis in Matrigel and can reconstitute the MG in vivo. Further, we demonstrate that the loss of function in placode regulators LEF1 and TBX3 in mESCs results in impaired skin and MEMO generation. In summary, our MEMO model is a robust tool for studying the development of ectodermal appendages, and it provides a foundation for regenerative medicine and disease modeling.

Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies.

BACKGROUND: Diets high in n-3 long chain polyunsaturated fatty acids (LCPUFA) may modulate the development of IgE-mediated allergic disease and have been proposed as a possible allergy prevention strategy. The aim of this study was to determine whether n-3 LCPUFA supplementation of pregnant women reduces IgE-mediated allergic disease in their children. METHODS: Follow-up of children (n = 706) at hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome randomized controlled trial. The intervention group (n = 368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks' gestation until birth; the control group (n = 338) received matched vegetable oil capsules without n-3 LCPUFA. The diagnosis of allergic disease was made during medical assessments at 1 and 3 years of age. RESULTS: No differences were seen in the overall percentage of children with IgE-mediated allergic disease in the first 3 years of life between the n-3 LCPUFA and control groups (64/368 (17.3%) vs 76/338 (22.6%); adjusted relative risk 0.78; 95% CI 0.58-1.06; P = 0.11). Eczema was the most common allergic disease; 13.8% of children in the n-3 LCPUFA group had eczema with sensitization compared with 19.0% in the control group (adjusted relative risk 0.75; 95% CI 0.53-1.05; P = 0.10). CONCLUSIONS: Overall, n-3 LCPUFA supplementation during pregnancy did not significantly reduce IgE-associated allergic disease in the first 3 years of life. Further studies should examine whether the nonsignificant reductions in IgE-associated allergies are of clinical and public health significance.