Effect of Maxillary Osteotomy on Speech in Cleft Lip and Palate: Instrumental Outcomes of Velopharyngeal Function

Objective: To investigate the effect of maxillary osteotomy on velopharyngeal function in cleft lip and palate (CLP) using instrumental measures. / Design: A prospective study. / Participants: A consecutive series of 20 patients with CLP undergoing maxillary osteotomy by a single surgeon were seen at 0 to 3 months presurgery (T1), 3 months (T2), and 12 months (T3) post-surgery. / Interventions: Nasalance was measured on the Nasometer II 6400. For videofluoroscopy and nasendoscopy data, visual perceptual ratings, for example, palatal lift angle (PLAn), and quantitative ratiometric measurements, for example, closure ratio (CRa), were made using a validated methodology and computer software. Reliability studies were undertaken for all instrumental measures. / Main Outcome Measures: Repeated measures analysis of variance (with time at 3 levels) for nasalance and each velar parameter. Planned comparisons across pairs of time points (T1-T2, T1-T3, and T2-T3) including effect sizes. / Results: A significant difference over time was found for nasalance (P = .001) and planned comparisons across pairs of time points were significant between T1 and T2 (P = .008), T1 and T3 (P = .002), but not between T2 and T3 (P = .459) providing evidence that maxillary osteotomy can impact on nasalance adversely and that the changes seen are permanent and stable. There were also significant differences over time for PLAn (P = .012) and CRa (P = −.059) and planned comparisons for both velar parameters reflected similar findings to those of nasalance. / Conclusions: Maxillary osteotomy can adversely affect velopharyngeal function in patients with CLP. The study provides evidence for a much earlier post-surgery review even as early as 3 months after surgery

Identifying Predictors of Acquired Velopharyngeal Insufficiency in Cleft Lip and Palate Following Maxillary Osteotomy Using Multiple Regression Analyses

Background: Maxillary osteotomy is typically undertaken to correct abnormal facial growth in cleft lip and palate. The surgery can cause velopharyngeal insufficiency resulting in hypernasality. This study aims to identify valid predictors of acquired velopharyngeal insufficiency following maxillary osteotomy by using a range of perceptual and instrumental speech investigations and multiple regression. / Methods: A prospective study was undertaken consisting of a consecutive series of patients with cleft lip and palate (N = 20) undergoing maxillary osteotomy by a single surgeon. Participants were seen at: 0 to 3 months pre-surgery (T1), 3-months (T2), and 12-months (T3) post-surgery. Hypernasality was rated using the cleft audit protocol for speech-augmented (CAPS-A) and visual analog scales, and nasalance was measured on the Nasometer II 6400. For lateral videofluorosopic and nasendoscopic images, visual perceptual ratings and quantitative ratiometric measurements were undertaken. Multiple regression analyses were undertaken to identify predictors. / Results: T3 models with hypernasality as the dependent variable were found to be a good fit and significant (eg, CAPS-A: R2 = 0.920, F(11,7) = 7.303, P = 0.007). Closure ratio (a quantitative ratiometric measurement) and proportion of palate contacting the posterior pharyngeal wall (a visual perceptual rating) were identified as significant predictors for the CAPS-A model (P = 0.030, P = 0.002)

Comparative transcriptome analysis of the metal hyperaccumulator Noccaea caerulescens

The metal hyperaccumulator Noccaea caerulescens is an established model to study the adaptation of plants to metalliferous soils. Various comparators have been used in these studies. The choice of suitable comparators is important and depends on the hypothesis to be tested and methods to be used. In high-throughput analyses such as microarray, N. caerulescens has been compared to non-tolerant, non-accumulator plants like Arabidopsis thaliana or Thlaspi arvense rather than to the related hypertolerant or hyperaccumulator plants. An underutilized source is N. caerulescens populations with considerable variation in their capacity to accumulate and tolerate metals. Whole transcriptome sequencing (RNA-Seq) is revealing interesting variation in their gene expression profiles. Combining physiological characteristics of N. caerulescens accessions with their RNA-Seq has a great potential to provide detailed insight into the underlying molecular mechanisms, including entirely new gene products. In this review we will critically consider comparative transcriptome analyses carried out to explore metal hyperaccumulation and hypertolerance of N. caerulescens, and demonstrate the potential of RNA-Seq analysis as a tool in evolutionary genomic

Metabolic changes in response to varying whole-grain wheat and rye intake

Epidemiological studies have shown associations between whole-grain intake and lowered disease risk. A sufficient level of whole-grain intake to reach the health benefits has not been established, and there is limited knowledge about the impact of whole-grain intake on metabolite levels. In this clinical intervention study, we aimed to identify plasma and urine metabolites associated with two different intake levels of whole-grain wheat and rye and to correlate them with clinical plasma biomarkers. Healthy volunteers (N = 68) were divided into two groups receiving either whole-grain wheat or whole-grain rye in two four-week interventions with 48 and 96 g/d of whole grains consumed. The metabolomics of the plasma samples was performed with UPLC–QTOF-MS. Plasma alkylresorcinols were quantified with GC-MS and plasma and urinary mammalian lignans with HPLC-ECD. The high-dose intervention impacted the metabolite profile, including microbial metabolites, more in the rye-enriched diet compared with wheat. Among the increased metabolites were alkylresorcinol glucuronides, sinapyl alcohol, and pipecolic acid betaine, while the decreased metabolites included acylcarnitines and ether lipids. Plasma alkylresorcinols, urinary enterolactone, and total mammalian lignans reflected the study diets in a dose-dependent manner. Several key metabolites linked with whole-grain consumption and gut microbial metabolism increased in a linear manner between the two interventions. The results reveal that an increase in whole-grain intake, particularly rye, is strongly reflected in the metabolite profile, is correlated with clinical variables, and suggests that a diet rich in whole grains promotes the growth and/or metabolism of microbes producing potentially beneficial microbial metabolites.Similar content being viewed by other

Protocol for the development and validation procedure of the managing the link and strengthening transition from child to adult mental health care (MILESTONE) suite of measures

Background: Mental health disorders in the child and adolescent population are a pressing public health concern. Despite the high prevalence of psychopathology in this vulnerable population, the transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) has many obstacles such as deficiencies in planning, organisational readiness and policy gaps. All these factors contribute to an inadequate and suboptimal transition process. A suite of measures is required that would allow young people to be assessed in a structured and standardised way to determine the on-going need for care and to improve communication across clinicians at CAMHS and AMHS. This will have the potential to reduce the overall health economic burden and could also improve the quality of life for patients travelling across the transition boundary. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) project aims to address the significant socioeconomic and societal challenge related to the transition process. This protocol paper describes the development of two MILESTONE transition-related measures: The Transition Readiness and Appropriateness Measure (TRAM), designed to be a decision-making aide for clinicians, and the Transition Related Outcome Measure (TROM), for examining the outcome of transition. Methods: The TRAM and TROM have been developed and were validated following the US FDA Guidance for Patient-reported Outcome Measures which follows an incremental stepwise framework. The study gathers information from service users, parents, families and mental health care professionals who have experience working with young people undergoing the transition process from eight European countries. Discussion: There is an urgent need for comprehensive measures that can assess transition across the CAMHS/AMHS boundary. This study protocol describes the process of development of two new transition measures: the TRAM and TROM. The TRAM has the potential to nurture better transitions as the findings can be summarised and provided to clinicians as a clinician-decision making support tool for identifying cases who need to transition and the TROM can be used to examine the outcomes of the transition process. Trial registration: MILESTONE study registration: ISRCTN83240263 Registered 23-July-2015 - ClinicalTrials.gov NCT03013595 Registered 6 January 2017

Metallothioneins 2 and 3 contribute to the metal-adapted phenotype but are not directly linked to Zn accumulation in the metal hyperaccumulator, Thlaspi caerulescens

To study the role of metallothioneins (MTs) in Zn accumulation, the expression of TcMT2a, TcMT2b, and TcMT3 was analysed in three accessions and 15 F3 families of two inter-accession crosses of the Cd/Zn hyperaccumulator Thlaspi caerulescens, with different degrees of Zn accumulation. The highest expression levels were found in the shoots of a superior metal-accumulating calamine accession from St Laurent le Minier, with >10-fold TcMT3 expression compared with another calamine accession and a non-metallicolous accession. Moreover, F3 sibling lines from the inter-accession crosses that harboured the MT2a or MT3 allele from St Laurent le Minier had higher expression levels. However, there was no co-segregation of TcMT2a or TcMT3 expression and Zn accumulation. To examine the functions of TcMTs in plants, TcMT2a and TcMT3 were ectopically expressed in Arabidopsis. The transformant lines had reduced root length in control medium but not at high metal concentrations, suggesting that the ectopically expressed proteins interfered with the physiological availability of essential metals under limited supply. The Arabidopsis transformant lines did not show increased tolerance to Cd, Cu, or Zn, nor increased Cd or Zn accumulation. Immunohistochemical analysis indicated that in roots, MT2 protein is localized in the epidermis and root hairs of both T. caerulescens and Arabidopsis thaliana. The results suggest that TcMT2a, TcMT2b, and TcMT3 are not primarily involved in Zn accumulation as such. However, the elevated expression levels in the metallicolous accessions suggests that they do contribute to the metal-adapted phenotype, possibly through improving Cu homeostasis at high Zn and Cd body burdens. Alternatively, they might function as hypostatic enhancers of Zn or Cd tolerance

Predictors of transitioning to adult mental health services and associated costs: a cross-country comparison

BACKGROUND: Young people are at risk of falling through the care gap after leaving child and adolescent mental health services (CAMHS) despite an ongoing need for mental health support. Currently, little is known about the predictors of transitioning to adult mental health services (AMHS), and associated healthcare and societal costs as young people cross the transition boundary. OBJECTIVE: To conduct a secondary data analysis exploring predictors of transitioning or falling through the gap and associated costs. METHODS: Data were used from a longitudinal study, which followed young people from seven European countries for 2 years after reaching their CAMHS boundary. Predictors of transitioning (including sociodemographic and clinical variables) and longitudinal resource use were compared for 488 young people who transitioned to AMHS versus those who fell through the gap. FINDINGS: Young people were more likely to transition to AMHS if they were severely ill. Those from Italy, the Netherlands and the UK were more likely to fall through the gap than transition to AMHS. Healthcare costs fell for all young people over the study, with a sharper decrease for those who fell through the gap. CONCLUSIONS: Total healthcare costs fell for all participants, indicating that the intensity of mental health support reduces for all young people as they cross the CAMHS boundary, regardless of clinical need. CLINICAL IMPLICATIONS: It is important that alternative forms of mental health support are available for young people who do not meet the AMHS care threshold but still have mental health needs after leaving CAMHS

Why do women invest in pre-pregnancy health and care? A qualitative investigation with women attending maternity services

Background Despite the importance attributed to good pre-pregnancy care and its potential to improve pregnancy and child health outcomes, relatively little is known about why women invest in pre-pregnancy health and care. We sought to gain insight into why women invested in pre-pregnancy health and care. Methods We carried out 20 qualitative in-depth interviews with pregnant or recently pregnant women who were drawn from a survey of antenatal clinic attendees in London, UK. Interviewees were purposively sampled to include high and low investors in pre-pregnancy health and care, with variation in age, partnership status, ethnicity and pre-existing medical conditions. Data analysis was conducted using the Framework method. Results We identified three groups in relation to pre-pregnancy health and care: 1) The “prepared” group, who had high levels of pregnancy planning and mostly positive attitudes to micronutrient supplementation outside of pregnancy, carried out pre-pregnancy activities such as taking folic acid and making changes to diet and lifestyle. 2) The “poor knowledge” group, who also had high levels of pregnancy planning, did not carry out pre-pregnancy activities and described themselves as having poor knowledge. Elsewhere in their interviews they expressed a strong dislike of micronutrient supplementation. 3) The “absent pre-pregnancy period” group, had the lowest levels of pregnancy planning and also expressed anti-supplement views. Even discussing the pre-pregnancy period with this group was difficult as responses to questions quickly shifted to focus on pregnancy itself. Knowledge of folic acid was poor in all groups. Conclusion Different pre-pregnancy care approaches are likely to be needed for each of the groups. Among the “prepared” group, who were proactive and receptive to health messages, greater availability of information and better response from health professionals could improve the range of pre-pregnancy activities carried out. Among the “poor knowledge” group, better response from health professionals might yield greater uptake of pre-pregnancy information. A different, general health strategy might be more appropriate for the “absent pre-pregnancy period” group. The fact that general attitudes to micronutrient supplementation were closely related to whether or not women invested in pre-pregnancy health and care was an unanticipated finding and warrants further investigation.This report is independent research commissioned and funded by the Department of Health Policy Research Programme Pre-Pregnancy Health and Care in England: Exploring Implementation and Public Health Impact, 006/0068

PCR-based zebrafish model for personalised medicine in head and neck cancer

BackgroundCurrently, in vivo model for personalised cancer drug testing is challenging. A zebrafish larvae xenograft model has been applied in recent years to cancer research, particularly for drug testing purposes, showing promising results in drug testing against patient-derived tumour xenografts. Currently, these xenograft models apply imaging techniques to measure drug efficacy. However, this method carries several limitations, including timely imaging, thereby reducing the available number of tested fish and drugs. Here, we propose a PCR-based fast assay to evaluate drug efficacy in a zebrafish larvae xenograft model.MethodsWe tested two primary and corresponding metastatic head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived tongue cancer sample applying zebrafish larvae xenograft model. Cisplatin efficacy was tested using imaging technique and compared the results with PCR-based methods. Drug screening of eight compounds was applied on both cell lines and patient sample using PCR.ResultsIn a head-to-head comparison, all the three techniques (imaging, quantitative PCR, and droplet digital PCR) showed similar reduction of the cancer cells growth after cisplatin treatment. Using the quantitative PCR assay, we demonstrated a dose-dependent response of HNSCC cells to cisplatin. Drug screening results of four HNSCC cell lines and patient sample revealed different drug efficacy between tested cancer cells.ConclusionWe introduce a novel, easy, fast and cost-effective PCR-based in vivo zebrafish larvae assay to test the response of cell lines and clinical tumour samples to anti-cancer drugs. This method goes hand-by-hand with the commonly used imaging assay.</p