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Our purpose was to explore genetics health professionals’ (GHPs) expectations of primary care providers' (PCPs) role in genomic medicine now and in the future. Focus groups/interviews were conducted with GHPs in Ontario, Canada. Recordings were transcribed and analysed using qualitative descriptive analysis. Five focus groups (6 clinical geneticists, 24 genetic counselors, 1 nurse, 4 laboratory staff, 3 genetics program administrators) and 3 interviews (nurses) were conducted. GHPs described a key role for PCPs in genomic medicine that could be enhanced if GHPs and PCPs worked together more effectively, making better use of GHPs as a scarce specialist resource, improving PCP knowledge and awareness of genomics, and increasing GHPs’ understanding of primary care practice and how to provide PCPs meaningful education and support. Health system change is needed to facilitate the GHP/PCP relationship and improve care. This might include: PCPs ordering more genetic tests independently or with GHP guidance prior to GHP consultations, genomic expertise in primary care clinics or GHPs being accessible through buddy systems or virtually through telemedicine or electronic consultation, and developing educational materials and electronic decision support for PCPs. Our findings highlight need for change in delivering genomic medicine, which requires building the relationship between GHPs and PCPs, and creating new service delivery models to meet future needs.

Objective To use patient-guided tours to gain insight into the experiences of patients with disabilities receiving primary care, with the goal of suggesting improvements. Design A qualitative experience-based design study, using patient-guided tours. Setting Multidisciplinary academic urban primary care practice. Participants Patients with disabilities identified by their health care providers. Methods Patients walked through the clinic as they would on a “typical visit” describing their feelings and experiences. The investigator used a semistructured interview guide to prompt the patient. The tour was audiorecorded and transcribed. Thematic content analysis was used. Main findings Participants included 18 patients with various disabilities (physical disability, sensory disability, chronic illness, mental illness, learning disability, developmental disability). Strong positive relationships, particularly with the team and administrative staff, profoundly affected perceived access and experience of care. Multidirectional, clear, and respectful communication independently improved patients’ experiences dramatically. Participants said that many access, coordination, and physical barriers were eased by team relationships and communication. Physical space and building issues were troublesome for those with physical and mental disabilities alike. Each participant’s disability itself played a role in their experience but was not described as prominently as their relationship, communication, and spatial challenges. Participants described the patient-guided tour method as valuable to elicit experiences and feelings. Conclusion Some health care teams are unaware of how relationships and communication affect every aspect of health care for people with disabilities. Highlighting these findings with providers and organizations might prompt a more patient-centred model of care. Our experience-based design consisting of patient-guided tours was effective in assessing how those with disabilities experienced care.

Objective To explore primary care providers’ (PCPs’) preferred roles and confidence in caring for infants receiving a positive cystic fibrosis (CF) newborn screening (NBS) result, as well as management of CF family planning issues, given that expanded NBS has resulted in an increase in positive results. Design Mailed questionnaire. Setting Ontario. Participants Ontario FPs, pediatricians, and midwives identified by Newborn Screening Ontario as having had an infant with a positive CF NBS result in their practice in the previous 6 months. Main outcome measure Primary care providers’ preferred roles in providing well-baby care for infants with positive CF screening results. Results Overall, 321 of 628 (51%) completed surveys (208 FPs, 68 pediatricians, 45 midwives). For well-baby care for infants confirmed to have CF, 77% of PCPs indicated they would not provide total care (ie, 68% would share care with other specialists and 9% would refer to specialists completely); for infants with an inconclusive CF diagnosis, 50% of PCPs would provide total care, 45% would provide shared care, and 5% would refer to a specialist; for CF carriers, 89% of PCPs would provide total care, 9% would provide shared care, and 2% would refer. Half (54%) of PCPs were extremely or very confident in providing reassurance about CF carriers’ health. Only 25% knew how to order parents’ CF carrier testing; 67% knew how to refer for prenatal diagnosis. Confidence in reassuring parents about the health of CF carrier children was associated with providing total well-baby care for CF carriers (risk ratio of 1.50; 95% CI 1.14 to 1.97) and infants with an inconclusive diagnosis (risk ratio of 3.30; 95% CI 1.34 to 8.16). Conclusion Most PCPs indicated willingness to treat infants with a range of CF NBS results in some capacity. It is concerning that some indicated CF carriers should have specialist involvement and only half were extremely or very confident about reassuring families about carrier status. This raises issues about possible medicalization of those with carrier status, prompting the need for PCP education about genetic disorders and the meaning of genetic test results.

L.K. is a fellow in the Canadian Institutes of Health Research (CIHR) Strategic Training in Advanced Genetic Epidemiology (STAGE) programme and is supported by the CIHR Doctoral Research Award from the Frederick Banting and Charles Best Canada Graduate Scholarships (GSD-137441). Transdisciplinary Research for Cancer in Lung (TRICL) of the International Lung Cancer Consortium (ILCCO) was supported by the National Institutes of Health (U19-CA148127, CA148127S1). Genotyping for the TRICL-ILCCO OncoArray was supported by in-kind genotyping at Centre for Inherited Disease Research (CIDR) (26820120008i-0–6800068-1). Genotyping for the Head and Neck Cancer OncoArray performed at CIDR was funded by the US National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780–0. CAPUA study was supported by FIS-FEDER/Spain grant numbers FIS-01/310, FIS-PI03–0365 and FIS-07-BI060604, FICYT/Asturias grant numbers FICYT PB02–67 and FICYT IB09–133, and the University Institute of Oncology (IUOPA), of the University of Oviedo and the Ciber de Epidemiologia y Salud Publica. CIBERESP, SPAIN. The work performed in the CARET study was supported by the National Institute of Health (NIH)/National Cancer Institute (NCI): UM1 CA167462 (PI: Goodman), National Institute of Health UO1-CA6367307 (PIs Omen, Goodman); National Institute of Health R01 CA111703 (PI Chen), National Institute of Health 5R01 CA151989 (PI Doherty). The Liverpool Lung Project is supported by the Roy Castle Lung Cancer Foundation. The Harvard Lung Cancer Study was supported by the NIH (National Cancer Institute) grants CA092824, CA090578 and CA074386. The Multiethnic Cohort Study was partially supported by NIH Grants CA164973, CA033619, CA63464 and CA148127. The work performed in MSH-PMH study was supported by the Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to R.J.H. and G.L. and the Alan Brown Chair and Lusi Wong Programs at the Princess Margaret Hospital Foundation. The Norway study was supported by Norwegian Cancer Society, Norwegian Research Council. The work in TLC study has been supported in part the James & Esther King Biomedical Research Program (09KN-15), National Institutes of Health Specialized Programs of Research Excellence (SPORE) Grant (P50 CA119997) and by a Cancer Center Support Grant (CCSG) at the H. Lee Moffitt Cancer Center and Research Institute, an NCI designated Comprehensive Cancer Center (grant number P30-CA76292). The dataset(s) used for the analyses described were obtained from Vanderbilt University Medical Center’s BioVU, which is supported by institutional funding and by the Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH. Dr Melinda Aldrich is supported by the by NIH/National Cancer Institute 5K07CA172294. The Copenhagen General Population Study (CGPS) was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital. The NELCS study: Grant Number P20RR018787 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Kentucky Lung Cancer Research Initiative (KLCRI) was supported by the Department of Defense (Congressionally Directed Medical Research Program, U.S. Army Medical Research and Materiel Command Program) under award number: 10153006 (W81XWH-11–1-0781). Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense. This research was also supported by unrestricted infrastructure funds from the UK Center for Clinical and Translational Science, NIH grant UL1TR000117 and Markey Cancer Center NCI Cancer Center Support Grant (P30 CA177558) Shared Resource Facilities: Cancer Research Informatics, Biospecimen and Tissue Procurement, and Biostatistics and Bioinformatics. The research undertaken by M.D.T., L.V.W. and M.S.A. was partly funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. M.D.T. holds a Medical Research Council Senior Clinical Fellowship (G0902313). The Tampa study was funded by Public Health Service grants P01-CA68384 and R01-DE13158 from the National Institutes of Health. The University of Pittsburgh head and neck cancer case–control study is supported by US National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; grants 04/12054–9 and 10/51168–0). The authors thank all the members of the GENCAPO team. This publication presents data from the Head and Neck 5000 study. The study was a component of independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707–10034). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Human papillomavirus (HPV) serology was supported by a Cancer Research UK Programme Grant, the Integrative Cancer Epidemiology Programme (grant number: C18281/A19169). The Alcohol-Related Cancers and Genetic Susceptibility Study in Europe (ARCAGE) was funded by the European Commission’s fifth framework programme (QLK1– 2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte and Padova University (CPDA057222). The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) awards IG 2011 10491 and IG 2013 14220 to S.B. and by Fondazione Veronesi to S.B. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97–0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (01/01768–2). The IARC Central Europe study was supported by the European Commission’s INCO-COPERNICUS Program (IC15-CT98–0332), US NIH/National Cancer Institute grant CA92039 and World Cancer Research Foundation grant WCRF 99A28. The IARC Oral Cancer Multicenter study was funded by grant S06 96 202489 05F02 from Europe against Cancer; grants FIS 97/0024, FIS 97/0662 and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; the UICC Yamagiwa-Yoshida Memorial International Cancer Study; the National Cancer Institute of Canada; Associazione Italiana per la Ricerca sul Cancro; and the Pan-American Health Organization. Coordination of the EPIC study is financially supported by the European Commission (DG SANCO) and the International Agency for Research on Cancer.

Objective To investigate associations of adolescents’ time spent on homework/studying with nocturnal time for sleep and depression symptoms, in a competitive academic environment. Design Cross-sectional, anonymous survey of sleep habits, school life, and health-related measures. Setting Eight schools in Singapore. Participants Total 1225 adolescents aged 13–19 years. Measurements Self-reported sleep behavior and time use data were collected separately for school days and weekends. Multiple regression models were used to test covariation of time spent on homework/studying with other activities, and associations of homework/studying duration with depression symptoms. Results Time in bed for sleep and media use were inversely related with homework/studying duration on both school days and weekends, adjusting for time spent on other activities and demographic variables. Face-to-face family time and hanging out with friends were also reciprocally related with homework/studying duration on weekends. Depression scores were higher in adolescents who spent long hours on homework/studying. On school days, this was mediated by reduced time in bed for sleep. On weekends, homework/studying duration associated with depression symptoms, adjusting for time in bed and other covariates. Adolescents who spent ≥5 hours on homework/studying per day on weekends had greater symptoms of anhedonia and anxiety. Conclusions In a competitive academic setting, adolescents who spent more time on homework/studying spent less time on sleep, media use, and social activities. Independent of effects on sleep, long hours on homework/studying on weekends may be a risk factor for depression. Reducing adolescents’ workload outside of class may benefit their sleep, schoolwork-life balance, and mental well-being.

Adolescents throughout the world do not obtain adequate sleep. A recent proliferation of experimental and quasi-experimental studies on teens concur in finding that multiple successive nights of restricted sleep can impair multiple cognitive functions. These effects cumulate over successive nights, may not achieve complete restitution after weekend recovery sleep, and may even be compounded by re-exposure to sleep restriction. An hour-long afternoon nap reduces sleepiness and improves vigilance, memory encoding and mood without interfering with nocturnal sleep when the latter is deficient. The very technologies that disrupt sleep can be used to improve it by providing novel avenues to personalize sleep recommendations by monitoring the effects of deficient sleep duration, quality, regularity and continuity.

Study Objectives Gains in cognitive test performance that occur during adolescence are associated with brain maturation. Cortical thinning and reduced sleep slow wave activity (SWA) are markers of such developmental changes. Here we investigate whether they mediate age-related improvements in cognition. Methods 109 adolescents aged 15–19 years (49 males) underwent magnetic resonance imaging, polysomnography (PSG), and a battery of cognitive tasks within a 2-month time window. Cognitive tasks assessed nonverbal intelligence, sustained attention, speed of processing and working memory and executive function. To minimize the effect of sleep history on SWA and cognitive performance, PSG and test batteries were administered only after at least 8 nights of 9-h time-in-bed (TIB) sleep opportunity. Results Age-related improvements in speed of processing (r = 0.33, p = 0.001) and nonverbal intelligence (r = 0.24, p = 0.01) domains were observed. These cognitive changes were associated with reduced cortical thickness, particularly in bilateral temporoparietal regions (rs = −0.21 to −0.45, ps < 0.05), as well as SWA (r = −0.35, p < 0.001). Serial mediation models found that ROIs in the middle/superior temporal cortices, together with SWA mediated the age-related improvement observed on cognition. Conclusions During adolescence, age-related improvements in cognition are mediated by reductions in cortical thickness and sleep SWA.

In congenital vestibular disorders (CVDs), children develop an abnormal inner ear before birth and face postnatal challenges to maintain posture, balance, walking, eye-hand coordination, eye tracking, or reading. Only limited information on inner ear pathology is acquired from clinical imaging of the temporal bone or studying histological slides of the temporal bone. A more comprehensive and precise assessment and determination of the underlying mechanisms necessitate analyses of the disorders at the cellular level, which can be achieved using animal models. Two main criteria for a suitable animal model are first, a pathology that mirrors the human disorder, and second, a reproducible experimental outcome leading to statistical power. With over 40 genes that affect inner ear development, the phenotypic abnormalities resulting from congenital vestibular disorders (CVDs) are highly variable. Nonetheless, there is a large subset of CVDs that form a common phenotype of a sac-like inner ear with the semicircular canals missing or dysplastic, and discrete abnormalities in the vestibular sensory organs. We have focused the review on this subset, but to advance research on CVDs we have added other CVDs not forming a sac-like inner ear. We have included examples of animal models used to study these CVDs. Presently, little is known about the central pathology resulting from CVDs at the cellular level in the central vestibular neural network, except for preliminary studies on a chick model that show significant loss of second-order, vestibular reflex projection neurons.

Mageu is a fermented, non-alcoholic maize-derived product unique to southern Africa. The aim of this study was to identify the health benefits of a polyphenolic extract of commercially produced mageu related to the antioxidant properties and effects on lipid accumulation in differentiated 3T3-L1 adipocytes. A pooled sample of mageu Number 1 brand (original non-flavored) was subjected to in vitro gastroduodenal digestion (GDD). Reverse phase high-performance liquid chromatography of unfractionated undigested (UD) and GDD mageu revealed that with digestion there was an increased extraction of 1.2, 1.83, 1.45, 4.86, and 3.17-fold of caffeic acid, 3,4-dihydroxybenzoic acid, p-coumaric acid, 4 hydroxybenzoic acid and ferulic acid, respectively. An associated increase in the total phenolic acid content and antioxidant activity in the3 kDa fraction was obtained. In contrast with digestion, inhibition of advanced glycation end products formation and low-density lipoprotein oxidation was found in the30 kDa fraction indicating the contribution of larger, possibly feruloylated polysaccharides, to activity. Cellular antioxidant activity in Caco-2 cells was90% for all UD fractions, but with GDD was reduced. All fractions had low scavenging of nitric oxide in the lipopolysaccharide/murine cell model. Exposure of 3T3-L1 adipocytes to all the UD and GDD mageu fractions (at 1% and 10% concentrations) during differentiation resulted in at least a 35% reduction in lipid accumulation, which was not associated with a loss of cellular viability. In conclusion, mageu, UD, and subjected to GDD contains phenolic acids with beneficial bioactive properties that contribute to antioxidant activity and reduces lipid accumulation in adipocytes. PRACTICAL APPLICATIONS: Mageu is a non-alcoholic fermented maize product which when digested has increased bioactivity. Its reported health benefits are due to its caloric content therefore the practical application of this research is to validate the scientific benefits of this food and encourage increased consumption of this functional food. This is especially important in the context of the South African population where this product is widely consumed as increasing obesity is associated with an increased risk of non-communicable disease. Furthermore, as a non-alcoholic drink, consumption can be promoted for all ages' groups and religions, and a commercialized manufacture processes can be optimized to increase phenolic acid release.

The African pumpkin (Momordica balsamina) contains bioactive phenolic compounds that may assist in reducing oxidative stress in the human body. The leaves are mainly consumed after boiling in water for a specific time, this hydrothermal process and conditions of the gastrointestinal tract may affect the presence and bioactivity of phenolics either positively or negatively. In this study, the effects of hydrothermal processing (boiling) and in vitro simulated human digestion on the phenolic composition, bioaccessibility and bioactivity in African pumpkin were investigated in comparison with those of spinach (Spinacia oleracea). A high-resolution ultra-performance liquid chromatography, coupled with diode array detection, quadrupole time-of-flight and mass spectrometer (UPLC-DAD-QTOF-MS) was used to profile phenolic metabolites. Metabolites such as 3-caffeoylquinic acid, 5-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid were highly concentrated in the boiled vegetable extracts compared to the raw undigested and all digested samples. The majority of African pumpkin and spinach extracts (non-digested and digested) protected Deoxyribonucleic acid (DNA), (mouse fibroblast) L929 and human epithelial colorectal adenocarcinoma (Caco-2) cells from 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative damage. From these results, the consumption of boiled African pumpkin leaves, as well as spinach, could be encouraged, as bioactive metabolites present may reduce oxidative stress in the body.

STUDY OBJECTIVES: To compare the quality and consistency in sleep measurement of a consumer wearable device and a research-grade actigraph with polysomnography (PSG) in adolescents. METHODS: Fifty-eight healthy adolescents (aged 15–19 years; 30 males) underwent overnight PSG while wearing both a Fitbit Alta HR and a Philips Respironics Actiwatch 2 (AW2) for 5 nights, with either 5 hours or 6.5 hours time in bed (TIB) and for 4 nights with 9 hours TIB. AW2 data were evaluated using two different wake and immobility thresholds. Discrepancies in estimated total sleep time (TST) and wake after sleep onset (WASO) between devices and PSG, as well as epoch-by-epoch agreements in sleep/wake classification, were assessed. Fitbit-generated sleep staging was compared to PSG. RESULTS: Fitbit and AW2 under default settings similarly underestimated TST and overestimated WASO (TST: medium setting (M10) ≤ 38 minutes, Fitbit ≤ 47 minutes; WASO: M10 ≤ 38 minutes; Fitbit ≤ 42 minutes). AW2 at the high motion threshold setting provided readings closest to PSG (TST: ≤ 12 minutes; WASO: ≤ 18 minutes). Sensitivity for detecting sleep was ≥ 90% for both wearable devices and further improved to 95% by using the high threshold (H5) setting for the AW2 (0.95). Wake detection specificity was highest in Fitbit (≥ 0.88), followed by the AW2 at M10 (≥ 0.80) and H5 thresholds (≤ 0.73). In addition, Fitbit inconsistently estimated stage N1 + N2 sleep depending on TIB, underestimated stage N3 sleep (21–46 min), but was comparable to PSG for rapid eye movement sleep. Fitbit sensitivity values for the detection of N1 + N2, N3 and rapid eye movement sleep were ≥ 0.68, ≥ 0.50, and ≥ 0.72, respectively. CONCLUSIONS: A consumer-grade wearable device can measure sleep duration as well as a research actigraph. However, sleep staging would benefit from further refinement before these methods can be reliably used for adolescents. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: The Cognitive and Metabolic Effects of Sleep Restriction in Adolescents; Identifier: NCT03333512; URL: https://clinicaltrials.gov/ct2/show/NCT03333512 CITATION: Lee XK, Chee NIYN, Ong JL, Teo TB, van Rijn E, Lo JC, Chee MWL. Validation of a consumer sleep wearable device with actigraphy and polysomnography in adolescents across sleep opportunity manipulations. J Clin Sleep Med. 2019;15(9):1337–1346.

Lynch syndrome (LS) is the most common inherited cause of colorectal cancer. Although testing all colorectal tumors for LS is recommended, the uptake of reflex-testing programs within health systems has been limited. This multipronged study describes the design of a provincial program for reflex testing in Ontario, Canada. We recruited key stakeholders to participate in qualitative interviews to explore the barriers and facilitators to the implementation of a reflex-testing program. Data were analyzed in an iterative manner, key themes identified, and a framework for a proposed program developed. Twenty-six key informants participated in our interviews, and several themes were identified. These included providing education for stakeholders (patients, primary care providers, surgeons); challenges with sustaining various resources (laboratory costs, increased workload for pathologists); ensuring consistency of reporting test results; and developing a plan to measure program success. Using these themes, a framework for the reflex-testing program was developed. At a subsequent stakeholder meeting, the framework was refined, and recommendations were identified. This study identifies factors to ensure the effective implementation of a population-level program for reflex LS testing. The final product is a prototype that can be utilized in other jurisdictions, taking into account local environmental considerations.

Sleep benefits prospective memory in young adults probably in part due to its well-established role in enhancing declarative memory, thereby facilitating retrieval of the intention content. In prior work on adolescents, we did not detect differences in prospective memory comparing five nights of sleep restriction and adequate sleep. Here, we examined whether this might be attributed to a limited role of sleep in benefiting the declarative content in this age group, and whether a sleep benefit on prospective memory would be uncovered with a shorter retention interval.A total of 59 adolescents (mean ± standard deviation: 16.55 ± 0.94 years) were instructed to remember to press a special key in response to two target words embedded in a semantic categorization task. Memory was tested after a 12-h retention interval, which included either overnight sleep (21:00-09:00, n = 29) or daytime wakefulness (09:00-21:00, n = 30).We found no significant group difference in the percentage of target words correctly responded to (mean ± standard error of the mean for the sleep group: 32.76 ± 6.69%; wake group: 41.67 ± 7.61%, t = 0.88, p = 0.38). However, participants who slept recalled more target words compared to those who stayed awake (98.28 ± 1.72% vs. 86.67 ± 5.32%, t = 2.05, p 0.05). In addition, a significantly greater proportion of sleep participants (n = 28 of 29) compared to wake participants (n = 24 of 30) recalled both target words correctly (χThese findings suggest that during adolescence, sleep plays a more prominent role in improving memory for the content as compared to the execution of intentions.

The purpose of the study was to quantify the frequency, severity, and location of patellofemoral (PF) articular cartilage changes recurrent patellar instability treated surgically in patients with preoperative clinical patellar crepitation.A single-surgeon database was queried for all knees with recurrent patellar instability between 3/2000 and 6/2012 (n=214). Only knees which underwent knee arthroscopy during the surgical treatment were included (n=148). PF articular cartilage condition was assessed arthroscopically.There were 148 knees in 130 patients (mean age, 16 y), which met inclusion criteria. There were 93 females and 37 males. Diagnoses were dislocations [122 (82.4%)] and subluxations (26). Preoperatively 28 knees (18.9%) had PF crepitation. Statistical analysis demonstrated preoperative PF crepitation was correlated with medial patellar facet lesions (P=0.0022) and were 3.6 times more likely to have medial patellar facet lesions. Crepitation was correlated with the higher outerbridge (OB) patellar grades (P0.0001) and larger patellar lesion size (P=0.0021). At arthroscopy 89 knees (60.5%) had patellar articular cartilage damage with a mean OB grade of 1.3 (0 to 4) and mean size of 93.2 mm (0 to 750). The femoral articular cartilage was identified in 29 knees (19.7%) with a mean OB grade of 0.44 (0 to 4).PF articular damage was present in 63% of knees, which were surgically treated for patellar instability. The patella was involved in 61% (mean, 129 mm) and femoral trochlea in 20% (mean 166 mm) of knees. Knee with preoperative PF crepitation (20% of cohort) more commonly had medial patellar facet lesions with higher OB grades, and larger patellar lesion size than knees without preoperative crepitation. Because of the high frequency of patellar (83%) and femoral (36%) articular damage documented at the time of surgical reconstruction, visualization of the PF joint is recommended when knees have preoperative PF crepitation.Level IV.

Objective To explore primary care providers’ (PCPs’) role in result notification for newborn screening (NBS) for cystic fibrosis (CF), given that expanded NBS has increased the number of positive screening test results, drawing attention to the role of PCPs in supporting families. Design Cross-sectional survey and qualitative interviews. Setting Ontario. Participants Primary care providers (FPs, pediatricians, and midwives) who received a positive CF NBS result for an infant in their practice in the 6 months before the study. Main outcome measures Whether the PCP notified the family of the initial positive CF screening result. Results Data from 321 PCP surveys (response rate of 51%) are reported, including 208 FPs, 68 pediatricians, and 45 midwives. Interviews were completed with 34 PCPs. Most (65%) surveyed PCPs reported notifying the infant’s family of the initial positive screening result; 81% agreed that they have an important role to play in NBS; and 88% said it was important for PCPs, rather than the NBS centre, to notify families of initial positive results. With support and information from NBS centres, 68% would be extremely or very confident in doing so; this dropped to 54% when reflecting on their recent reporting experience. More than half (58%) of all PCPs said written point-of-care information from the NBS centre was the most helpful format. Adjusted for relevant factors, written educational information was associated with a lower rate of notifying families than written plus verbal information (risk ratio of 0.79; 95% CI 0.69 to 0.92). In the interviews, PCPs emphasized the challenge of balancing required content knowledge with the desire for the news to come from a familiar provider. Conclusion Most PCPs notify families of NBS results and value this role. These data are relevant as NBS programs and other genomic services expand and consider ways of keeping PCPs confident and actively involved.

Primary care providers will increasingly be tasked with managing most secondary findings from genomic sequencing, but literature exploring their capacity to manage findings beyond conventional genetic testing is limited. This study aimed to explore primary care providers' challenges and potential solutions for managing secondary findings. Providers were recruited in two groups. Group 1 providers had a patient in their practice who received secondary findings and all potential group 1 providers were invited to participate. Group 2 providers were provided with the secondary findings of a hypothetical patient and were purposefully sampled for maximal variation in sex, practice setting, and geographic location. Providers were interviewed about their challenges and solutions managing secondary findings from a patient in their practice or a hypothetical patient. Using interpretive description methodology, transcripts were analysed thematically complemented by constant comparison. Out of the fifty-five providers invited, 15 family physicians participated across community and academic settings in Ontario, Canada (range 6-40 years in practice; 10/15 female). Providers described a responsibility to manage secondary findings, but limited capacity for this, describing practice, knowledge, and technical challenges. Providers expressed concern that compared to other incidental findings, secondary genomic findings might be reported directly to patients and result in longer-term anxiety. Potential solutions were a structured letter with categorized results and summary tables highlighting key secondary findings with follow-up recommendations and resources, as well as electronic medical records (EMRs) that store and integrate genomic information for prescribing or referrals. These solutions were deemed essential to address knowledge and technical challenges faced by primary care physicians and ultimately promote clinical utility of secondary findings.

Most secondary genomic findings (SFs) fall in the scope of primary care practice. However, primary care providers' (PCPs) capacity to manage these findings is not well understood. We explored PCPs' views and experiences of managing SFs through a qualitative study. PCPs participated in semi-structured interviews about SFs from a patient in their practice or a hypothetical patient. The interpretive descriptive methodology was used to analyze transcripts thematically through constant comparison. Fifteen family physicians from Ontario, Canada participated (ten females; 6-40 years in practice across community and academic settings). PCPs made sense of SFs through the lens of actionability: they actively looked for clinical relevance by considering a wide range of immediate and future actions, including referrals, genetic testing, screening, lifestyle changes, counseling about family planning, informing family members, future medication choice, increased vigilance/surveillance, and managing results in the electronic medical record. PCPs saw clinical actionability as the main benefit mitigating the potential harms of learning SFs, namely patient anxiety and unnecessary investigations. PCPs conceptualized actionability more broadly than it is traditionally defined in medical genetics. Further research will be needed to determine if PCPs' emphasis on actionability conflicts with patients' expectations of SFs and if it leads to overutilization of healthcare resources.

Study Objectives Existing literature suggests that sleep-dependent memory consolidation is impaired in older adults but may be preserved for personally relevant information. Prospective memory (PM) involves remembering to execute future intentions in a timely manner and has behavioral importance. As previous work suggests that N3 sleep is important for PM in young adults, we investigated if the role of N3 sleep in PM consolidation would be maintained in older adults. Methods Forty-nine young adults (mean age ± SD: 21.8 ± 1.61 years) and 49 healthy older adults (mean age ± SD: 65.7 ± 6.30 years) were randomized into sleep and wake groups. After a semantic categorization task, participants encoded intentions comprising four related and four unrelated cue-action pairs. They were instructed to remember to perform these actions in response to cue words presented during a second semantic categorization task 12 h later that encompassed either daytime wake (09:00 am–21:00 pm) or overnight sleep with polysomnography (21:00 pm–09:00 am). Results The significant condition × age group × relatedness interaction suggested that the sleep benefit on PM intentions varied according to age group and relatedness (p = 0.01). For related intentions, sleep relative to wake benefitted young adults’ performance (p < 0.001) but not older adults (p = 0.30). For unrelated intentions, sleep did not improve PM for either age group. While post-encoding N3 was significantly associated with related intentions’ execution in young adults (r = 0.43, p = 0.02), this relationship was not found for older adults (r = −0.07, p = 0.763). Conclusions The age-related impairment of sleep-dependent memory consolidation extends to PM. Our findings add to an existing body of work suggesting that the link between sleep and memory is functionally weakened in older adulthood.

We investigated whether variable sleep schedules might mitigate the neurobehavioural deficits induced by multiple nights of sleep restriction. In this 4-night experiment, 78 young adults (age: 18-28 years) were randomly assigned to four groups: 8888, 8666, 8846 and 8486, where each digit corresponded to time-in-bed in hours for each study night. After one baseline night of 8-hr time-in-bed, time-in-bed remained unchanged for the 8888 group, while the other groups had short sleep schedules (total time-in-bed = 18 hr) that differed in the number of time-in-bed changes. Sleep was monitored using actigraphy at home. Daytime neurobehavioural functions were assessed in the laboratory at single time points, after the baseline night, and again after 3 nights of the sleep manipulation period. For sustained attention, the 8888 group responded faster in the Psychomotor Vigilance Task after the manipulation period (p = .01), while responses became slower for the less variable sleep schedules (8666 and 8846; p .01), but not the most variable sleep schedule (8486; p = .14). Processing speed also improved in the 8888 group and the variable 8846 and 8486 groups (p .01), but not in the stable 8666 group (p = .09). Furthermore, subjective sleepiness was preserved in the 8888 and, importantly, 8486 groups (p .05), but was elevated in the 8666 and 8846 groups (p .05). These findings suggest that when sleep opportunities are limited across multiple nights, a variable sleep schedule that allows for prophylactic and/or recovery sleep on some nights may mitigate some daytime neurobehavioural deficits as compared with a schedule with no opportunity for recovery.

Family history (FH) of a first-degree relative with colorectal cancer (CRC) is associated with two to fourfold increased risk, yet screening uptake is suboptimal despite proven mortality reduction. We developed a FH-based CRC Risk Triage/Management tool for family physicians (FPs), and educational booklet for patients with CRC FH. This report describes physician referral and patient screening behavior 5 and 10 years post-educational intervention, and factors associated with screening. Longitudinal cohort study. FPs/patients in Ontario and Newfoundland, Canada were sent questionnaires at baseline (2005), 5 and 10 years (2015) following tool/booklet receipt. FPs were asked about CRC screening, patients about FH, screening type and timing. “Correct” screening was concordance with tool recommendations. Results reported for 29/121 (24%) FPs and 98/297 (33%) patients who completed all 3 questionnaires. Over 10 years 2/3 patients received the correct CRC screening test at appropriate timing (baseline 75%, 5-year 62%, 10-year 65%). About half reported their FP recommended CRC screening (5-year 51%, 10-year 63%). Fewer than half the patients correctly assessed their CRC risk (44%, 40%, 41%). Patients were less likely to have correct screening timing if female (RR 0.78; 95% CI 0.61, 0.99; p = 0.045). Patients were less likely to have both correct test and timing if moderate/high CRC risk (RR 0.66; 95% CI 0.47, 0.93; p = 0.017) and more likely if their physician recommended screening (RR1.69; 95% CI 1.15, 2.49; p = 0.007). Physician discussion of CRC risk and screening can positively impact patient screening behavior. Efforts are particularly needed for women and patients at moderate/high CRC risk.

Study Objectives We compared the basic cognitive functions of adolescents undergoing split (nocturnal sleep + daytime nap) and continuous nocturnal sleep schedules when total sleep opportunity was either below or within the recommended range (i.e. 6.5 or 8 h). Methods Adolescent participants (age: 15–19 year) in the 8-h split (n = 24) and continuous (n = 29) sleep groups were compared with 6.5-h split and continuous sleep groups from a previous study (n = 58). These protocols involved two baseline nights (9-h time-in-bed [TIB]), 5 nights of sleep manipulation, 2 recovery nights (9-h TIB), followed by a second cycle of sleep manipulation (3 nights) and recovery (2 nights). Cognitive performance, subjective sleepiness, and mood were evaluated daily; sleep was assessed using polysomnography. Results Splitting 6.5 h of sleep with a mid-afternoon nap offered a boost to cognitive function compared to continuous nocturnal sleep. However, when total TIB across 24 h increased to 8 h, the split and continuous sleep groups performed comparably in tests evaluating vigilance, working memory, executive function, processing speed, subjective sleepiness, and mood. Conclusions In adolescents, the effects of split sleep on basic cognitive functions vary by the amount of total sleep obtained. As long as the total sleep opportunity across 24 h is within the recommended range, students may fulfill sleep requirements by adopting a split sleep schedule consisting of a shorter period of nocturnal sleep combined with a mid-afternoon nap, without significant impact on basic cognitive functions. Clinical trial registration NCT04044885.

PurposeThis study investigated nicotine dependence as an independent risk factor for upper aerodigestive tract (UADT) cancers, including lung and head and neck cancers (HNC). The study aimed to isolate the direct effect of nicotine dependence, independent of tobacco smoking.MethodsA case-control study with a total of 4957 participants was conducted in Ontario, Canada, of which 2964 categorized as either current or former smokers were used in the analysis. Nicotine dependence of ever-smokers (2360 UADT cases and 604 controls) was measured using the Fagerström Test for Nicotine Dependence. Using mediation analyses and adjusted logistic regression models, we decomposed the direct effect of nicotine dependence and the mediated effect of smoking duration to quantify the risks of lung and HNC. The role of human papillomavirus (HPV) and cancer subtypes were assessed.ResultsMost individual nicotine dependence behaviours showed positive associations with lung cancer with approximately 1.8 to 3.5-fold risk increase, and to lesser extent with 1.4 to 2.3-fold risk for HNC. Nicotine dependence is partially accountable for increased risks of lung cancer (OR = 1.20, 95%CI = 1.13-1.28) and HNC (1.12, 95%CI = 1.04-1.19). Nicotine dependence had a greater effect on the risk of HPV-negative oropharyngeal cancer (OR = 3.06, 95%CI = 1.65-5.66) in comparison to HPV-positive oropharyngeal cancer (OR = 1.05, 95%CI = 0.67-1.65). The direct effects of nicotine dependence remained significant after accounting for cumulative tobacco exposures.ConclusionNicotine dependence increases the risks of lung and HNC cancers after accounting for tobacco smoking, suggesting potential toxic effects of nicotine. These results are informative for the safety consideration of nicotine exposures.

Many developmental disorders of the inner ear are manifested clinically as delayed motor development and challenges in maintaining posture and balance, indicating involvement of central vestibular circuits. How the vestibular circuitry is rewired in pediatric cases is poorly understood due to lack of a suitable animal model. Based on this, our lab designed and validated a chick embryo model to study vestibular development in congenital vestibular disorders. The developing inner ear or “otocyst” on the right side of 2-day-old chick embryos (E2) was surgically rotated 180° in the anterior–posterior axis, forming the “anterior–posterior axis rotated otocyst chick” or ARO chick. The ARO chick has a reproducible pathology of a sac with truncated or missing semicircular canals. A sac is the most common inner ear defect found in children with congenital vestibular disorders. In E13 ARO chicks, the sac contained all three cristae and maculae utriculi and sacculi, but the superior crista and macula utriculi were shortened in anterior–posterior extent. Also, the number of principal cells of the tangential vestibular nucleus, a major avian vestibular nucleus, was decreased 66 % on the rotated side. After hatching, no difference was detected between ARO and normal chicks in their righting reflex times. However, unlike normal chicks, ARO hatchlings had a constant, right head tilt, and after performing the righting reflex, ARO chicks stumbled and walked with a widened base. Identifying the structure and function of abnormally developed brain regions in ARO chicks may assist in improving treatments for patients with congenital vestibular disorder.

BACKGROUND Excessive femoral anteversion is a developmental condition that can become symptomatic into adolescence and manifest as anterior knee pain, tripping, and or problems with sports. Femoral derotational osteotomy about an antegrade intramedullary nail (IMN) is an accepted option to treat this condition. This is the first report of the clinical and functional outcomes of treatment of excessive anteversion with femoral derotational osteotomy stabilized with an IMN. METHODS We prospectively enrolled 28 consecutive patients between 2013 and 2014 who underwent derotational osteotomy. Physical examination measures were used to calculate the amount of angular correction with focus on internal and external rotation of the hip, as well as the trochanteric prominence angle test of femoral anteversion. The International Knee Documentation Committee-9, Marx, and Tegner activity scales were 3 patient-reported outcomes recorded. RESULTS After femoral derotation osteotomy over an IMN, femoral anteversion, as measured by the trochanteric prominence angle, improved an average of 29 degrees (P

In spinal deformity surgery, posterior column osteotomies (PCOs) are used to increase spinal flexibility and permit greater deformity correction, while avoiding the morbidity of anterior column surgery. Complications related to use of PCOs have been well characterized in adults; however, there is a paucity of information in the pediatric population. A single-surgeon retrospective analysis was completed of 484 PCOs in 142 patients (average age: 14.5 years) undergoing spinal deformity surgery. All surgeries were completed by a standard posterior approach using a midline incision and dual-rod, pedicle screw constructs. PCO-related complications were recorded (intraoperative monitoring alerts, postoperative neurologic deficit, dural tear/violations, cerebrospinal fluid [CSF] leak, pseudarthrosis, etc.) and analyzed by diagnosis (idiopathic, congenital, neuromuscular, syndromic). The diagnoses for the 142 patients were idiopathic (103 patients), neuromuscular (23 patients), syndromic (14 patients), and congenital (2 patients). In a subset of 87 patients with 2-year radiographic follow-up, the preoperative major coronal Cobb measurement was 75.5° ± 17.6°, which corrected to 34.9° ± 17.5° postoperatively and 37.8° ± 17.9° at last follow-up (p < .0001, p < .0001). Complications evaluated were postoperative neurologic deficit (0% of patients, 0/142), dural tears/violations at site of PCO (0.4% of PCOs, 2/484), CSF leak (0% of patients, 0/142), and pseudoarthrosis at site of PCO (0% of PCOs, 0/290). The overall frequency of complications related to PCOs was 0.4% (0.4% dural tears/violations) with 0% postoperative neurologic deficit, CSF leak, or pseudarthrosis. Based on these data, PCOs appear to be a safe technique in pediatric spine deformity surgery, with a low rate of technique-related complications. Retrospective case series. To report the frequency of posterior column osteotomy complications (neurologic deficit, dural tear, cerebrospinal fluid leak, and pseudarthrosis) in pediatric patients undergoing spinal deformity surgery. Level IV.

Sleep disturbance is common in late life. While social interaction is a basic human concern, few studies have explored the linkage between interpersonal relationships and sleep disturbance. The present study examines the reciprocal associations between weak social networks outside the household and sleep disturbance in elderly, as well as the underlying mechanisms. We utilized data from a nationally representative longitudinal survey of community-dwelling elderly in Singapore (n = 1417; ≥ 60 years). Participants were assessed three times over 6 years (2009, 2011, 2015). Measures included strength of social networks outside the household, restless sleep (sleep disturbance), and the mediating variables of depressed mood, chronic diseases, and cognitive impairment. A cross-lagged mediation analysis was conducted. Bootstrapping results showed that weaker social networks were related to more restless sleep via more depressed mood. Also, restless sleep was negatively associated with social networks through depressed mood. The other mediators examined were not significant. Weak social networks and restless sleep reciprocally influence each other through depressed mood. Recognition of this interplay can inform efforts in improving elderly’s sleep quality, social networks, and psychological well-being.

Prospective memory is defined as remembering to do something at a particular moment in the future and may be modulated by sleep. Here, we investigated whether multiple nights of partial sleep deprivation would affect the successful retrieval of intentions. Fifty-nine adolescents (mean age ± SD: 16.1 ± 0.6 years) were instructed to remember to press specific keys in response to the target words presented during a semantic categorization task in the future. Their memory was tested after five nights of either 5-h (sleep restriction group) or 9-h time-in-bed (control group). The average percentage of target words correctly responded to was small and did not significantly differ between the two groups (mean ± SEM for the sleep restriction group: 15.52 ± 6.61%; the control group: 23.33 ± 7.48%, p = 0.44). Thus, after the extended retention interval, prospective remembering was poor and did not appear to be affected by post-learning sleep restriction. These findings suggest a temporal boundary beyond which intentions fall below requisite levels of activation, potentially masking any benefits for retrieval conferred by sleep.

Background The Ontario Breast Screening Program (OBSP) expanded in July 2011 to screen high‐risk women aged 30–69 with annual MRI and mammography. This study evaluated wait time (WT) indicators along the genetic assessment (GA) pathway for women referred to the High Risk OBSP. Methods Information was collected for 27,170 women referred to the High Risk OBSP from July 2011 to June 2015 and followed for GA until June 2016. Median duration (days), interquartile range (IQR) were measured for each WT indicator by program year, age, prior breast cancer, and risk criteria. Results Among 24,811 women who completed GA, 16,367 (66.0%) had genetic counseling only, 8,444 (34.0%) had counseling and testing and 8,027 (32.4%) met the high risk criteria. Median WT from physician visit to first screen was longer for women having genetic counseling only compared to those having counseling and testing (244 vs. 197 days). Women having counseling only also experienced the longest WT from physician visit to genetic counseling (88 days; IQR = 10–174), which increased by year from 71 to 100 days (p

The effect of simulated in vitro upper gut digestion on the phenolic composition and antioxidant properties of processed cowpea beans was studied. The samples comprised four cowpea cultivars: a cream, brownish-cream and two reddish-brown cultivars. Dry cowpea seeds were soaked in water, blended into paste and deep-fried in vegetable oil. The fried samples were taken through in vitro upper gut digestion followed by freeze-drying of the supernatant. Phenolic composition of extracts from the supernatants were determined using HPLC-MS. Radical scavenging activities were documented using the TEAC, ORAC and nitric oxide (NO) assays. In vitro digestion of the processed cowpeas resulted in phenolic-peptide complexes that were identified for the first time, and decreased extractable phenolic compounds. However, the radical scavenging activities increased. The processed cowpeas and their digests inhibited cellular NO production, and oxidative DNA and cellular damage. In conclusion, deep-fried cowpeas when consumed, could potentially help alleviate oxidative stress-related conditions.

Background:Aging is accompanied by cognitive decline that is escalated in older adults reporting extreme sleep duration. Social relationships can influence health outcomes and thus may qualify the association between sleep duration and cognitive function. The present study examines the moderating effects of marital status, household size, and social network with friends and relatives on the sleep–cognition association among older adults.Methods:Data (N = 4,169) came from the Social Isolation, Health, and Lifestyles Survey, a nationally representative survey of community-dwelling older Singaporeans (≥ 60 years). Sleep duration and social relationships were self-reported. Cognitive function was assessed with the Short Portable Mental Status Questionnaire.Results:Regression analysis revealed that the inverted U-shaped association between sleep duration and cognitive function was less profound among older adults who were married (vs. unmarried) and those who had stronger (vs. weaker) social networks. In contrast, it was more prominent among individuals who had more (vs. fewer) household members.Conclusions:Being married and having stronger social networks may buffer against the negative cognitive impact of extreme sleep duration. But larger household size might imply more stress for older persons, and therefore strengthen the sleep duration–cognitive function association. We discuss the potential biological underpinnings and the policy implications of the findings. Although our findings are based on a large sample, replication studies using objective measures of sleep duration and other cognitive measures are needed.

Population-based reflex testing of colorectal tumors can identify individuals with Lynch syndrome (LS), but there is debate regarding the type of patient discretion such a program warrants. We examined health-care providers’ views and experiences to inform the design of a reflex-testing program and their perspectives regarding an opt-out option. We interviewed providers managing LS or colorectal cancer patients, including surgeons, genetic counselors, oncologists, primary-care physicians, and gastroenterologists. Qualitative data were analyzed thematically using constant comparison techniques. Providers supported a reflex-testing program because of the current lack of coordinated immunohistochemistry (IHC) testing and underascertainment of LS patients as well as the opportunity to standardize the increasing use of genomic tests in practice. Most supported an opt-out after reflex testing because they felt that IHC is akin to other pathology tests, which are not optional. Some favored an opt-out before testing because of concern for patients experiencing distress, insurance discrimination, or a diagnostic odyssey that may be inconclusive. Providers support a reflex-testing program to improve the identification and management of suspected LS patients. However, how to support meaningful information provision to enable an opt-out without jeopardizing testing uptake and the anticipated public health benefits remains a policy challenge. Genet Med advance online publication 06 October 2016

Background:Durations of nocturnal sleep and daytime nap influence the well-being of older adults. It is thus essential to understand their determinants. However, much previous research did not assess sleep duration and nap duration individually, and longitudinal data is lacking. This study aimed at examining the impact of demographic, psychosocial, and health factors, including ethnicity, social networks outside the household, smoking and physical exercise on sleep duration and nap duration among community-dwelling elderly.Methods:Our study involved over 2,600 older adults (≥60 years) from a longitudinal, nationally representative survey – the Panel on Health and Ageing of Singaporean Elderly. Sleep and nap durations at Time 2 (two years later) were regressed on predictors measured at Time 1.Results:Time 2 short nocturnal sleep duration was predicted by Malay ethnicity (relative to Chinese and Indian), older age, lower education level, more depressive symptoms, and obesity, whereas future long nocturnal sleep duration was predicted by weaker social networks, older age, and more chronic diseases. Furthermore, smoking, obesity, Malay or Indian (relative to Chinese), older age, male gender, and cognitive impairment predicted longer daytime nap duration in the future.Conclusions:Older adults’ nocturnal sleep and daytime nap durations may be affected by different demographic, psychosocial, and health factors. Thus, it is important to differentiate these two attributes in this age group.

Achievement-oriented adolescents often study long hours under conditions of chronic sleep restriction, adversely affecting cognitive function. Here, we studied how napping and rest breaks (interleaved off-task periods) might ameliorate the negative effects of sleep restriction on processing speed. Fifty-seven healthy adolescents (26 female, age = 15-19 years) participated in a 15-day live-in protocol. All participants underwent sleep restriction (5 h time-in-bed), but were then randomized into two groups: one of these groups received a daily 1-h nap opportunity. Data from seven of the study days (sleep restriction days 1-5, and recovery days 1-2) are reported here. The Blocked Symbol Decoding Test, administered once a day, was used to assess time-on-task effects and the effects of rest breaks on processing speed. Controlling for baseline differences, participants who took a nap demonstrated faster speed of processing and greater benefit across testing sessions from practice. These participants were also affected significantly less by time-on-task effects. In contrast, participants who did not receive a nap benefited more from the rest breaks that were permitted between blocks of the test. Our results indicate that napping partially reverses the detrimental effects of sleep restriction on processing speed. However, rest breaks have a greater effect as a countermeasure against poor performance when sleep pressure is higher. These data add to the growing body of evidence showing the importance of sleep for good cognitive functioning in adolescents, and suggest that more frequent rest breaks might be important in situations where sleep loss is unavoidable.

Ilex guayusa tea preparations are now commercially available as Runa tea. Little is known regarding the antioxidant and anti-inflammatory bioactivities of this tea. The I. guayusa teas had a total polyphenolic content between 54.39 and 67.23 mg GAE per g dry mass and peroxyl radical scavenging capacities between 1773.41 and 2019 μmol TE per g dry mass, nearly half of that for the Camellia sinensis teas. The I. guayusa teas afforded 60-80% protection from oxidative stress in the Caco-2 cellular antioxidant assay, comparable to the C. sinensis teas. The anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 cells of I. guayusa teas was similarly comparable to the C. sinensis teas with nitric oxide production reduced by 10-30%. Major compounds identified by mass spectrometry were the phenolic mono- and dicaffeoylquinic acid derivatives. I. guayusa teas are a good source of dietary phenolic compounds with cellular antioxidant and anti-inflammatory properties.

Introduction Mindfulness-based training has shown potential in reducing anxious and ruminative thoughts before sleep, and improving sleep quality. However, traditional 8-week programs have limited acceptability and uptake. In this study, we aimed to test the effects of a short introductory mindfulness training course on pre-sleep arousal and sleep quality. Methods Enrollees in a 4-week Mindfulness Foundation Course were invited to participate in the study and were allocated to one of two groups: intervention (N = 57) and waitlist control (N = 39). 101 participants enrolled in the experiment and 96 completed the protocol (mean(sd) age = 49.5(1.5), 56 female). Participants completed the Pittsburgh Sleep Quality Inventory (PSQI) and the pre-sleep arousal scale (PSAS), and were monitored by actigraphy for a week at baseline and post-intervention. To test the effect of the intervention, outcome variables were subjected to repeated-measures ANCOVA with group as a between-subject variable, and age, gender, and years of education as covariates using intent-to-treat analysis. Results PSQI scores improved across both groups (treatment: t56=4.25, p Conclusion The study suggests that a 4-week introductory mindfulness course has moderate effects on reducing cognitive arousal prior to sleep, and that these effects are correlated with improvements in subjective sleep quality. Support This study was funded from a STaR investigator grant (NMRC/STaR/0015/2013) and the National Research Foundation (Singapore) Science of Learning Grant (NRF2016-SOL002-001).

Previously Os, a 22 amino acid sequence of a defensin from the soft tick Ornithodoros savignyi, was found to kill Gram-positive and Gram-negative bacteria at low micromolar concentrations. In this study, we evaluated synthetic peptide analogues of Os for antibacterial activity with an aim to identify minimalized active peptide sequences and in so doing obtain a better understanding of the structural requirements for activity. Out of eight partially overlapping sequences of 10 to 12 residues, only Os(3-12) and Os(11-22) exhibit activity when screened against Gram-positive and Gram-negative bacteria. Carboxyamidation of both peptides increased membrane-mediated activity, although carboxyamidation of Os(11-22) negatively impacted on activity against Staphylococcus aureus. The amidated peptides, Os(3-12)NH2 and Os(11-22)NH2 , have minimum bactericidal concentrations of 3.3 μM against Escherichia coli. Killing was reached within 10 minutes for Os(3-12)NH2 and only during the second hour for Os(11-22)NH2 . In an E. coli membrane liposome system, both Os and Os(3-12)NH2 were identified as membrane disrupting while Os(11-22)NH2 was less active, indicating that in addition to membrane permeabilization, other targets may be involved in bacterial killing. In contrast to Os, the membrane disruptive effect of Os(3-12)NH2 did not diminish in the presence of salt. Neither Os nor its amidated derivatives caused human erythrocyte haemolysis. The contrasting killing kinetics and effects of amidation together with structural and liposome leakage data suggest that the 3-12 fragment relies on a membrane disruptive mechanism while the 11-22 fragment involves additional target mechanisms. The salt-resistant potency of Os(3-12)NH2 identifies it as a promising candidate for further development.

Introduction: Preparing primary care providers for genomic medicine (GM) first requires assessment of their educational needs in order to provide clear, purposeful direction and justify educational activities. More understanding is needed about primary care providers’ perspectives on their role in newer areas of GM and what resources would be helpful in practice. Our objective was to determine family physicians’ (FP) current involvement and confidence in GM, attitudes regarding its clinical value, suggestions for integration of GM into practice, and resources and education required. Methods: A self-complete anonymous questionnaire was mailed to a random sample of 2,000 FPs in Ontario, Canada in September 2012. Results: Adjusted response rate was 26% (361/1,365), mean age was 51, and 53% were male. FPs reported many aspects of traditional GM as part of current practice (eliciting family history: 93%; deciding who to refer to genetics: 94%; but few reported confidence (44%, 32% respectively). Newer areas of GM were not part of most FPs’ current practice and confidence was low (pharmacogenetics: 28% part of practice, 5% confident; direct-to-consumer genetic testing: 14%/2%; whole genome sequencing: 8%/2%). Attitudes were mixed with 59% agreeing that GM would improve patient health outcomes, 41% seeing benefits to genetic testing, but only 36% agreeing it was their responsibility to incorporate GM into practice. Few could identify useful sources of genetic information (22%) or find information about genetic tests (21%). Educational resources participants anticipated would be useful included contact information for local genetics clinics (89%), summaries of genetic disorders (86%), and genetic referral (85%) and testing (86%) criteria. About 58% were interested in learning about new genetic technologies. Most (76%) wanted to learn through in-person teaching (lectures, seminars etc.), 66% wanted contact with a local genetic counselor to answer questions, and 59% were interested in a genetics education website. Conclusion: FPs lack confidence in GM skills needed for practice, particularly in emerging areas of GM. They see their role as making appropriate referrals, are somewhat optimistic about the contribution GM may make to patient care, but express caution about its current clinical benefits. There is a need for evidence-based educational resources integrated into primary care and improved communication with genetic specialists.

Children with congenital vestibular disorders show delayed motor development and challenges in maintaining posture and balance. Computed tomography images reveal that these children have abnormal inner ears in the form of a sac, with the semicircular canals missing or truncated. Little is known about how this inner ear abnormality affects central vestibular development. At present, mice with the chromodomain helicase DNA-binding protein 7 mutation are the most common model for studying congenital vestibular disorders, despite forming multiple diverse inner ear phenotypes and inducing abnormal cerebellar and visual system development. To identify the effects of a sac-like inner ear on central vestibular development, we have designed and implemented a new model, the anterior-posterior axis rotated otocyst (ARO) chick, which forms a sac-like inner ear in 85% of cases. The ARO chick is produced by anterior-posterior rotation of the otocyst at embryonic day 2. Here, we describe for the first time the 15% of ARO chicks that form three small semicircular canals and rename the ARO chicks forming sacs (ARO/s chicks). The basic features of the vestibular sensory organs in ARO/s chicks are similar to those found in patients’ sacs, and ARO/s hatchlings experience balance and walking problems like patients. Thus, ARO/s chicks have a reproducible inner ear phenotype without abnormalities in vestibular-related structures, making the model a relatively simple one to evaluate the relationship between the sac-like inner ear pathology and formation of the central vestibular neural circuitry. Here, we describe unpublished details on the surgical approaches to produce ARO chicks, including pitfalls and difficulties to avoid. NEW & NOTEWORTHY This paper describes simple techniques for chick otocyst rotation resulting in a sac-like inner ear (85%), the common phenotype in congenital vestibular disorders. We now describe anterior-posterior axis rotated otocyst chicks, which form three small canals (15%), and rename chicks forming a sac (ARO/s chicks). Basic protocols and potential complications of otocyst rotation are described. With the use of ARO/s chicks, it will be possible to determine how the vestibular neural circuit is modified by sac-like inner ear formation.

Surgical-site infections are one of the most concerning complications in patients treated with growing rods (GR). The purpose of this study was to evaluate the use of preoperative screening for Staphylococcus aureus (SA) for all growing spine procedures, and if this would permit alteration of prophylactic antibiotics to cover the identified resistances.All patients were identified who had SA screening during the course of GR treatment. In otal, 34 patients [23 neuromuscular (NMS), 4 congenital, 4 idiopathic scoliosis (IS), and 3 syndromic] were identified who had 111 preoperative screenings [79 lengthenings, 23 insertions, 6 revisions, and 3 conversions to posterior spinal fusions (PSF)]. Mean age at GR insertion was 5.5 years (2 to 11 y).There were 11 methicillin-resistant Staphylococcus aureus (MRSA) "+" screenings in 6 patients (5 NMS, 1 IS): 3 in 3 patients before GR insertion and 8 in 3 patients (all 3 were negative at GR insertion screening) at subsequent surgeries. There were 23 methicillin-sensitive Staphylococcus aureus (MSSA) "+" screenings in 12 patients (7 NMS, 2 congenital, 2 IS, 1 syndromic): 2 in 2 patients before GR insertion and 21 in 10 patients at subsequent surgeries (18 lengthenings, 3 revisions). Overall, 13 patients (3 MRSA+10 MSSA) were initially negative but screened positive for the first time at a subsequent surgery (12 lengthenings, 1 GR to PSF). All patients (n=5) with positive screenings before GR insertion were in patients with NMS (3 MRSA, 2 MSSA). On the basis of sensitivities, 9 patients demonstrated SA resistance to cefazolin (8 MRSA and 1 MSSA) and 6 to clindamycin (5 MRSA and 1 MSSA). Hence, if cefazolin was routinely used for all patients 26.5% of patients (9/34) would have been inadequately covered at some point during their GR treatment; clindamycin, 17.7% (6/34).The use of SA nasal swab screening in GR patients identified 9 patients (26.5%) whose prophylactic antibiotics (cefazolin) could be altered to permit appropriate SA coverage.Level IV-retrospective case series.

Objectives Shortened sleep has negative consequences on adolescents’ well-being. The present study evaluated an interactive school-based sleep education program (SEP) aimed at increasing adolescent sleep duration. Design and intervention A cluster-randomized controlled trial with 12 clusters (classes) was used. The intervention group received a SEP and the active control group received a healthy living program (HLP). Both groups underwent a 4-week class-based education program. The SEP students learned about the importance of sleep, the barriers to getting enough sleep, and how to improve their time management to increase their sleep opportunity. The HLP students learned about various health-related topics not including sleep. Participants A total of 210 students (mean age = 14.04 ± 0.32 years) were randomly assigned to the SEP (n = 102) or the HLP (n = 108) group, with 6 classes per group. Measurements Sleep (actigraphically measured), sleep knowledge, and time usage were assessed using linear mixed models at three time points: baseline, immediately after intervention, and 1-month follow-up. Results Sleep knowledge improved at follow-up in the SEP relative to the HLP group (p = .017). Although students were receptive of the program and self-reported the intention to create more time for sleep, no changes in sleep were found following the SEP. Some benefit may have been masked by exam preparations at the follow-up evaluation. Conclusions Sleep education alone may not be sufficient to change sleep behavior. A combination of sleep education, starting school later, and parental involvement may be needed to encourage and enable changes in adolescent sleep duration.

Prior reports on geographical differences in sleep duration have relied on samples collected at different time points with a variety of subjective instruments. Using sleep data from a total of 553,559 nights from 23,680 Fitbit users (aged 15–80y), we found objective evidence for regional disparities in sleep duration of 32–43 min between Oceanian and East Asian users on weekdays. This was primarily driven by later bedtimes in East Asians. Although users in all countries extended sleep on weekends, East Asians continued to sleep less than their Oceanian counterparts. Women generally slept more than men, and older users slept less than younger users. Reasons for shorter sleep duration in East Asians on both weekdays and weekends, across the lifespan and in both sexes remain to be investigated.