Mutation of the conserved late element in geminivirus CP promoters abolishes Arabidopsis TCP24 transcription factor binding and decreases H3K27me3 levels on viral chromatin.

In geminiviruses belonging to the genus Begomovirus, coat protein (CP) expression depends on viral AL2 protein, which derepresses and activates the CP promoter through sequence elements that lie within the viral intergenic region (IR). However, AL2 does not exhibit sequence-specific DNA binding activity but is instead directed to responsive promoters through interactions with host factors, most likely transcriptional activators and/or repressors. In this study, we describe a repressive plant-specific transcription factor, Arabidopsis thaliana TCP24 (AtTCP24), that interacts with AL2 and recognizes a class II TCP binding site in the CP promoter (GTGGTCCC). This motif corresponds to the previously identified conserved late element (CLE). We also report that histone 3 lysine 27 trimethylation (H3K27me3), an epigenetic mark associated with facultative repression, is enriched over the viral IR. H3K27me3 is deposited by Polycomb Repressive Complex 2 (PRC2), a critical regulator of gene expression and development in plants and animals. Remarkably, mutation of the TCP24 binding site (the CLE) in tomato golden mosaic virus (TGMV) and cabbage leaf curl virus (CaLCuV) CP promoters greatly diminishes H3K27me3 levels on viral chromatin and causes a dramatic delay and attenuation of disease symptoms in infected Arabidopsis and Nicotiana benthamiana plants. Symptom remission is accompanied by decreased viral DNA levels in systemically infected tissue. Nevertheless, in transient replication assays CLE mutation delays but does not limit the accumulation of viral double-stranded DNA, although single-stranded DNA and CP mRNA levels are decreased. These findings suggest that TCP24 binding to the CLE leads to CP promoter repression and H3K27me3 deposition, while TCP24-AL2 interaction may recruit AL2 to derepress and activate the promoter. Thus, a repressive host transcription factor may be repurposed to target a viral factor essential for promoter activity. The presence of the CLE in many begomoviruses suggests a common scheme for late promoter regulation.

What influences decisions to donate plasma? A rapid review of the literature.

BACKGROUND AND OBJECTIVES: Plasma has become an essential ingredient for various medical treatments. Many blood collection agencies rely on voluntary non-remunerated donation when collecting plasma, but at present many do not collect sufficient plasma to meet domestic demands. This rapid review sought to explore the factors that have been found to influence people's decisions to donate plasma to inform future research. METHODS: Searches were conducted in PubMed, PsycINFO, Social Sciences Citation Index and CINAHL for peer-reviewed journal articles that discussed plasma donation and the factors associated with donor behaviour. Pertinent information from included articles was extracted and arranged in themes. RESULTS: In total, 33 articles were included in this review. Three main themes were identified by the authors. The first focused on site-level factors related to blood collection agencies' engagement with plasma donors and their influence on plasma donation experiences. The second theme considered how individual characteristics and experiences influence willingness to donate plasma. The third theme examined social and cultural-level factors, such as how social networks and community shape perceptions and experiences with donation. CONCLUSION: Our findings suggest that the current understanding of plasma donation is focused mainly on converting whole blood donors and also centres on individual-level factors to donation. Further research must examine what factors attract non-whole blood donors to become plasma donors, focusing on broader social-level influences. This review will inform policies and interventions for blood collection agencies to increase plasma donors.

What do you mean, 'negotiating?': Patient, physician, and healthcare professional experiences of navigating hierarchy in networks of interprofessional care.

Interprofessional collaborative practice is a phenomenon that can be fraught with power dynamics between professions, within professions, and between professionals and patients. In the literature, the dominant notion is that conflicting viewpoints and interests arising from unequal power dynamics can be resolved through negotiation. This study examined COPD patients, health professionals, and physician experiences of negotiation within 10 interprofessional collaborative COPD care teams. Physicians, patients, and healthcare professionals each had strikingly different conceptions and experiences of negotiating their perspective with other team members. Our study suggests that negotiation is an idealized notion rather than a relational process embedded in interprofessional collaborative practice. Importantly, we found that the ability and opportunity to negotiate one's perspective is heavily influenced by one's position in the workplace division of labor and professional hierarchy. We conclude that "negotiation" is only one approach among many in navigating interprofessional relations. Further, the rhetorical and ideological appeal of "negotiation" may overstate its role in interactions in interprofessional care settings, and lead to a misunderstanding of the power dynamics at play. It may be naïve to assume team members can control their situation through the competitive assertion of their individual perspective in a rational debate. Unfortunately, adopting the language of negotiation uncritically may not offer relevant solutions to structural and collective problems within a healthcare workplace.

Physico-chemical properties of an innovative gluten-free, low-carbohydrate and high protein-bread enriched with pea protein powder.

The study aimed to determine the effect of pea protein powder on the pasting behavior and physico-chemical properties including the composition of amino and fatty acids of gluten-free bread with low-carbohydrate content. The control bread recipe was based on buckwheat flour (50 g) and flaxseed flour (50 g) as main flours. Additionally, the improving additives for this control bread such as psyllium husk (4 g), potato fiber (2 g), and guar gum (2 g) were used. The mixture of base flour was supplemented with the addition of pea protein powder (PPP) in the amount ranging from 5 to 25%. The results of Visco analyzes measured by RVA apparatus showed that the addition of 10% PPP to the control bread did not significantly differentiate peak viscosity and pasting temperature which was at the level 3115 cP and 3149 cP and 50 °C, respectively. Supplementation of low-carbohydrate bread with 10% of PPP was acceptable and significantly increased the content of all analyzed amino acids, as well as the amount of α-linolenic acid concerning the control bread. The lowest value of chemical score was observed for leucine. The EAAI (essential amino acid index) value increased from 34 to 40 when the optimal protein supplement was added. The developed gluten-free, low-carbohydrate, and high protein bread was characterized by contents of carbohydrate of 16.9%, protein of 17.1%, fiber of 13.7%, fat of 3.3% and its calorific value was 194 kcal/100 g.

Macro and meso level influences on distributed integrated COPD care delivery: a social network perspective.

BACKGROUND: Care guidelines for people with chronic obstructive pulmonary disease (COPD) recommend an integrated approach for holistic, flexible, and tailored interventions. Continuity of care is also emphasised. However, many patients with COPD experience fragmented care. Discontinuities in healthcare and related social services are likely to result in disjointed rather than integrated care which can negatively affect patient health outcomes. The purpose of this qualitative study was to improve our understanding of, and how, contextual features pertaining to structures and processes of COPD integrated care influence delivery of care within patients' healthcare networks. METHODS: We conducted individual interviews with 28 participants (9 patients, 16 healthcare professionals, and 3 spousal caregivers). Participants were recruited through the lung clinic at a city hospital in western Canada. We employed a social network paradigm to analyse and interpret the data. RESULTS: The analysis revealed an overarching theme of fragmented COPD care with two sub-themes: (1) Funding shortfalls and availability of resources, and (2) Dis(mis)connected communication pathways. The overarching theme depicts variations, delays, and discontinuities in patient care. The sub-themes describe how macro level influences and meso level shortfalls were perceived to influence the availability of respiratory care resources that contributed to fragmented COPD care. CONCLUSIONS: Employing a social network lens drew particular attention to family physicians' pivotal role in delivering community-based COPD care. While an integrated approach to care is recommended by care guidelines, institutional and organizational structures and processes, such as financial and communication structures, may inhibit delivery of integrated care. Thus, macro and meso level structures and processes have the potential to shape patient care by constraining family physicians' purposive and communication actions necessary for facilitating an integrated distributed approach to care. We propose a context of care which fosters a context for family physicians' delivery of patient-centered care. Integrated care delivery may improve patients' wellbeing and alleviate financial constraints on the healthcare system.

Timing of Furlow Palatoplasty for Patients With Submucous Cleft Palate.

BACKGROUND: Submucous cleft palate (SMCP) is the most common form of cleft involving the posterior palate, resulting in variable degrees of velar dysfunction and speech disturbance. Although early surgical intervention is indicated for patients with true cleft palate, the indications for palatoplasty and timing of surgical intervention for patients with SMCP remain controversial. METHODS: Twenty-nine patients with SMCP were retrospectively reviewed. Patients treated with Furlow palatoplasty were dichotomized based on patient age at the time of surgical correction into early speech development and late speech development. Primary outcome measures included standardized assessments of hypernasal resonance and quantitative pre- and postoperative nasometry scores. Patients managed nonoperatively were included for comparison of early and late speech outcomes. RESULTS: Both early and late groups demonstrated improvement in qualitative assessment of hypernasal resonance following Furlow palatoplasty. Early and late groups also had significant improvement in pre- to postoperative nasometry scores from 7.4 to 2.3 SD from norm ( P = .01) and 6.0 to 3.6 SD from norm ( P = .02), respectively. There was no difference in postoperative nasometry scores between early and late groups, 2.3 and 3.6 SD ( P = .12). CONCLUSION: Furlow palatoplasty significantly improves the degree of hypernasality in patients with SMCP based on pre- and postoperative nasometry scores and on qualitative assessment of hypernasality. There were no differences in speech outcomes based on early compared with late operative intervention. Therefore, early palatal repair is not obligatory for optimal speech outcomes in children with SMCP and palatoplasty should be deferred until the emergence of overt velopharyngeal insufficiency.

Obstructive sleep apnea pretreatment and posttreatment in symptomatic children with congenital craniofacial malformations.

STUDY OBJECTIVES: Obstructive sleep symptoms are common in children with craniofacial malformations (CFM). However objective data about obstructive sleep apnea (OSA) is still limited. The aims of this study were to investigate the frequency of OSA in symptomatic children with CFM and to determine improvement in severity of OSA after treatment. METHODS: Symptomatic children with CFM referred for a diagnostic polysomnogram (PSG) were identified. Obstructive sleep apnea was defined as an apnea/hypopnea index (AHI) ≥ 1, with moderate/severe OSA as an AHI ≥ 5. RESULTS: Overall, 151 symptomatic children were identified; 87% were diagnosed with OSA, of whom 24% had moderate-to-severe OSA. Children with syndromic CFM, compared to non-syndromic CFM, were more likely to have an AHI ≥ 5 (syndromic 33% vs. non-syndromic 15%, p = 0.02). Of the 131 children with OSA, 64 were treated and 32 returned for a posttreatment PSG, with 22 treated with either positive airway pressure (PAP) or adenotonsillectomy (AT). Children treated with PAP demonstrated a decrease in AHI from 6.2 to 3.5 (p = 0.057) and an increase in SpO2 from 89.1% to 91.1% (p = 0.091). There were no significant improvements for those in the AT group for either AHI (2.5 to 1.8, p = 0.19) or SpO2 (90.4% to 91.3%, p = 0.46). Normalization of the AHI (AHI < 1) occurred in only one child in each group (7% and 14% of the PAP and AT groups, respectively). CONCLUSIONS: The vast majority of children with CFM referred for OSA evaluation are found to have objective evidence of OSA and a quarter of children have moderate-to-severe OSA. It is likely that many children with underlying OSA are not identified and referred for evaluation. Residual OSA after treatment is common in children with CFM.

Association between symptoms of sleep-disordered breathing and speech in children with craniofacial malformations.

STUDY OBJECTIVE: Sleep-disordered breathing (SDB) and speech difficulties are common problems in children with craniofacial malformations (CFM). The present study was designed to investigate whether resonance issues identified during speech assessment are associated with parental report of SDB symptoms in children with CFM. METHODS: Children aged 2-18 years with congenital CFM attending at the Craniofacial Anomalies Program from March 2007 to April 2011 were screened for SDB symptoms using the Sleep-Related Breathing Disturbance Scale of the Pediatric Sleep Questionnaire. Speech evaluation, based on the Pittsburgh Weighted Speech Scale score, was the tool used to investigate velopharyngeal dysfunction (VPD) based on speech perceptual assessment. RESULTS: A total of 488 children with congenital CFM were included. Overall 81% were Caucasian and 24% were overweight/obese. Twenty-four percent of children screened positive for SDB and 35% had VPD. Children with VPD were no more likely to screen positive for SDB than children without VPD (26% vs. 23%, p = 0.38). However, children with previous sphincter pharyngoplasty (SP) were more likely to have hyponasality (51% vs. 12%, p = 0.0001) and reduced or absent nasal emission (33% vs. 16%, p = 0.008). In a logistic regression, the adjusted odds ratio for SDB for those with hyponasality was 2.10 (95%CI 1.21-3.61, p = 0.008) and for those with reduced or absent nasal emission was 1.75 (95%CI 1.06-2.88, p = 0.028). CONCLUSION: Symptoms of sleep disordered breathing are common in children with craniofacial malformations especially if they have undergone sphincter pharyngoplasty; many of these children can be identified by measures of resonance on routine speech evaluation.

Symptoms of sleep disordered breathing in children with craniofacial malformations.

STUDY OBJECTIVE: The purpose of this study was to investigate the frequency of sleep disordered breathing (SDB) symptoms in a clinical sample of children with congenital craniofacial malformations (CFM) followed at a tertiary medical center and non-selected for sleep problems. METHODS: Cross-sectional study of 575 children aged 2-18 years followed at the Craniofacial Anomalies Program between March 2007 and May 2011. The Sleep-Related Breathing Disturbance scale of the Pediatric Sleep Questionnaire was used to screen for SDB, snoring, and sleepiness. A cutoff value ≥ 0.33 of the total answered questions identified children with positive screening for SDB symptoms. RESULTS: Overall, 25% of children screened positive for SDB, 28% for snoring, and 20% for sleepiness. In children with non-syndromic CFM, those with Robin sequence had the highest frequency of SDB, snoring, and sleepiness (43%, 44%, and 38%, respectively). In children with syndromic CFM, velocardiofacial/ DiGeorge syndrome had the highest frequency of SDB and sleepiness (48% and 43%, respectively). Children with Treacher Collins had the highest frequency of snoring (83%). The presence of cleft palate was not associated with an increased frequency of SDB symptoms. Nevertheless, children with syndromic CFM, compared to those with non-syndromic CFM, had a higher SDB score (0.27 ± 0.21 vs.0.21 ± 0.19, p = 0.003) and were more likely to have sleepiness (26% vs. 18%, p = 0.05). CONCLUSIONS: Congenital craniofacial malformations in children are associated with high risk for SDB symptoms. Our findings should encourage a high index of suspicion for SDB in children with CFM, with a low threshold for further testing and close follow-up. CITATION: Moraleda-Cibrián M; Edwards SP; Kasten SJ; Berger M; Buchman SR; O'Brien LM. Symptoms of sleep disordered breathing in children with craniofacial malformations.

Identification of sequences required for AL2-mediated activation of the tomato golden mosaic virus-yellow vein BR1 promoter.

A 108 bp sequence has been identified in the tomato golden mosaic virus-yellow vein (yvTGMV) B component that is necessary and sufficient for AL2-mediated activation of the BR1 promoter. The sequence appears to have a bipartite arrangement, with elements located between -144 to -77 and -59 to -36 from the transcription start site, with both being required for activation by AL2. These sequences are located upstream of a TATA box and bind nuclear proteins from spinach, tomato and Arabidopsis. These sequences are also capable of binding Arabidopsis PPD2, which has been shown previously to interact with the yvTGMV coat protein (CP) promoter. We have identified two putative transcription factor-binding sites (CCAAT and GTGANTG10) that are conserved in sequences necessary for activation of the yvTGMV BR1, as well as the yvTGMV and cabbage leaf curl virus (CabLCV) CP promoters, which are all activated by AL2. The yvTGMV BR1 promoter exhibits AL2-independent expression in vascular tissue, similar to the yvTGMV, CabLCV and spinach curly top virus CP promoters. Together, this further confirms a common regulatory mechanism for AL2-mediated activation of bipartite begomovirus promoters.

Posterior pharyngeal fat grafting for velopharyngeal insufficiency.

Objective : To determine if autologous fat grafting to the posterior pharynx can reduce hypernasality in patients with cleft palate and mild velopharyngeal insufficiency (VPI). Design : Retrospective case series. Setting : Tertiary care center. Patients : Eleven patients with cleft palate status after palatoplasty (with or without secondary speech surgery) with nasendoscopic evidence of VPI. Interventions : Autologous fat was harvested and injected into the posterior pharynx under general anesthesia. Main Outcome Measures : Pre- and postoperative subjective, nasometry, and nasendoscopy data. Apnea-hypopnea indices (AHIs) were also assessed. Comparisons were made using Fisher's exact test, Student's t tests, and relative risk (RR) assessments. Results : An average of 13.1 mL of fat was injected (range: 5 to 22 mL). Mean follow-up was 17.5 months (range: 12 to 25 months). Statistically significant improvements in speech resonance were identified in nasometry (Zoo passage; p  =  .027) and subjective hypernasality assessment (p  =  .035). Eight of the patients (73%) demonstrated normal speech resonance after posterior pharyngeal fat grafting (PPFG) on subjective or objective assessment (p  =  .001). All five patients with previous secondary speech surgeries demonstrated normal speech resonance on similar assessment (RR  =  1.8; p  =  .13). Complete velopharyngeal closure was observed in seven patients on postoperative nasendoscopy. No changes in AHIs were observed (p  =  .581). Conclusion : PPFG may be best used as an adjunct to secondary speech surgery. In this series, PPFG was not accompanied by the negative sequelae of hyponasality, sleep apnea, or airway compromise.

Skew deviation as the initial manifestation of left paramedian thalamic infarction.

We describe a 73-year-old man who developed diplopia as the initial manifestation of a left thalamic infarction. By the time he reached the emergency department, clouded consciousness precluded localization of the lesion. Results of brain MRI were initially interpreted as negative. Ophthalmologic examination several hours later disclosed a small vertical ocular misalignment attributed to skew deviation. This finding led to careful scrutiny of the upper brainstem on MRI. Comparison of the diffusion, apparent diffusion coefficient, and exponential apparent diffusion coefficient MRI studies allowed a diagnosis of subtle left thalamic infarction. The recognition of skew deviation in this setting is important because it may be the most specific indicator of a brainstem lesion.

The effectiveness of an interactive small group diabetes intervention in improving knowledge, feeling of control, and behavior.

The objective of this study is to evaluate the effectiveness of a small group intervention in improving knowledge, feeling of control, and behaviors related to self-management of diabetes. The intervention includes educational content on diabetes self-management as well as discussion of attitudes, feelings, and motivations about living with diabetes. The authors randomized volunteers into an intervention group that participated in the small-group learning activity and a control group that received a diabetes self-care book. A survey was conducted by telephone before and after each intervention and the difference in change over time between the groups was assessed for each outcome. Compared to the control group, participants in the small-group activity reported significant changes on all three outcomes adjusting for demographic differences between the groups. Because facilitating the learning session does not require clinically trained personnel, this type of intervention could broaden the resources available to people with diabetes.

Decontaminating the nasal passages.

Nasal decontamination may be indicated when the anterior nasal passages are contaminated with highly radioactive material or radioactive material with either irritating or toxic properties. Nasal irrigation (wash, rinse, douche, lavage) is an established technique used for other conditions and can be applied in these cases. This paper discusses the rationale and use of nasal irrigation and how to perform the technique.

Health-related quality of life in children with craniofacial anomalies.

The purpose of this study was to examine parents' perceptions of the health and health-related quality of life in a series of children and adolescents with cleft and other craniofacial anomalies. The subjects for this prospective study were a consecutive series of 54 children and adolescents presenting to an outpatient craniofacial anomalies surgery clinic, ages 5 to 18 years (mean, 8.9 +/- 4.2 years), 50 percent with cleft lip and/or palate, 9 percent synostotic (two coronal, two bicoronal, and one sagittal), 17 percent syndromic (two Apert, one Crouzon, one Noonan, two Goldenhar, two Smith-Lemli-Opitz, and one brachio-oto-renal), and 24 percent with other diagnoses. Subjects were divided into two groups, those with primary cleft lip and/or palate and those with other craniofacial anomalies. Health and health-related quality of life were assessed with the Child Health Questionnaire version PF28, a reliable and valid 28-Likert-item questionnaire completed by parents and yielding physical and psychosocial status scale scores. Physical and psychosocial scale scores largely fell within normal limits for the subset of children with cleft lip and/or palate. There were significant group differences in parents' ratings of global health status, with greater health concerns noted in the non-cleft lip and/or palate group. There were no significant associations between either age or sex and physical or psychosocial health. Physical health, behavior, and psychological status were highly correlated. Using a health status and quality-of-life assessment instrument, findings indicate perceived health differences between groups with and without primary cleft lip and/or palate. In contrast to normative data with the Child Health Questionnaire, findings suggest that there is a significant association between perceived physical health and psychosocial adjustment in the population of children with craniofacial anomalies. The significant perceived health needs of the non-cleft lip and/or palate group and the association between physical health and psychological adjustment highlight the importance of the interdisciplinary nature of craniofacial teams.