Hyoid bone morphology in patients with isolated robin sequence - A case-control study utilizing 3D morphable models.

Background: Abnormalities of the hyoid bone are associated with impairment of oropharyngeal functions including feeding, swallowing, and breathing. Few studies have characterized anatomic abnormalities of the hyoid in patients with Robin sequence (RS), e.g. a less mineralized and voluminous hyoid. The purpose of this study was to compare normal hyoid bone morphology and hyoid bone morphology in children with isolated RS. Methods: Three-dimensional (3D) reconstructions of the hyoid bone were obtained from CT-imaging of children with RS and unaffected controls. A 3D morphable model was constructed using Principal Component Analysis (PCA). Partial least squares - Discriminant Analysis (PLS-DA) and multivariate analysis of variance (MANOVA) were used to characterize and compare hyoid shape differences between patients with RS and an age-matched control group. Results: The study included 23 subjects with RS (mean age 9.8 ± 10.3 months) and 46 age-matched control samples. A less voluminous hyoid was observed for the RS group with a larger lateral divergence of the greater horns compared to controls (MANOVA, p-value<0.001). The first shape variable from the PLS-DA model showed a significant correlation for the observed variance between the two groups (Spearman R = -0.56, p-value<0.001). The control samples and 151 CT-scans of subjects up to age 4 years were used to create a 3D morphable model of normal hyoid shape variation (n = 197, mean age 22.1 ± 13.1 months). For the normal 3D morphable model, a high degree of allometric shape variation was observed along the first principal component. Conclusions: The 3D morphable models provide a comprehensive and quantitative description of variation in normal hyoid bone morphology, and allow detection of distinct differences between patients with isolated RS and controls.

The relationship between klotho, testosterone, and sexual health parameters among US adult men.

BACKGROUND: Klotho is a pleotropic hormone involved in a multitude of biological processes necessary for healthy aging, and affords protection from adverse events such as cardiovascular disease, inflammation, and various cancers. Emerging evidence suggests that klotho is also an important component of biochemical pathways that regulate hormone balance, which may include those pathways governing testosterone production and men's sexual health, though data are limited and results are mixed. OBJECTIVE: Using a cohort of 767 men from the NHANES 2015-2016 survey cycle, we set out to quantify the association between serum klotho levels and serum testosterone levels, as well as clinical markers of men's sexual health (e.g., testosterone:estrogen ratio, bioavailable testosterone, and free testosterone). METHODS: Multivariable linear and logistic regression models while controlling for potential confounders were constructed to quantify the relationship between serum klotho and testosterone, as well as between serum klotho and odds of low testosterone (serum testosterone < 300 ng/dL). RESULTS: A positive association was observed between serum klotho and testosterone (ß = 0.18, p = 0.04). Serum klotho levels were also stratified into quartiles, and we observed statistically significant increases in testosterone for increasing quartile level of klotho using the first quartile as the reference group (ß = 90.51, p = 0.001, ß = 106.93, p = 0.002, ß = 95.33, p = 0.03 for quartiles 2, 3, and 4, respectively). The average testosterone values by quartiles of klotho were 306.9 ng/dL, 390 ng/dL, 409.3 ng/dL, and 436.6 ng/dL, respectively. We modeled important proxies for sexual health including bioavailable and free testosterone, the testosterone:estradiol ratio, and C-reactive protein. Men in the second quartile of klotho had a significantly lower odds of an abnormal testosterone:estradiol ratio compared to the first quartile [OR = 0.18, 95% CI = (0.03, 0.98)].We observed null associations between continuous serum klotho and odds of low testosterone [OR = 1.0, 95% CI = (1.0, 1.0)], and when stratified by quartile, we observed a significant decrease in the odds of low testosterone for individuals in the second quartile of klotho compared to the first quartile [OR = 0.21, 95% CI = (0.05, 0.91)]. In addition, C-reactive protein was inversely associated with testosterone in men (ß = - 4.65, p = 0.001), and inversely associated with quartiles of klotho (ß = - 2.28, p = 0.04, ß = - 2.22, p = 0.04, ß = - 2.28, p = 0.03, for quartiles 2, 3, and 4, respectively). CONCLUSION: Our findings support previous studies suggesting a role for klotho in testosterone levels and sexual function among men. Future studies are warranted to corroborate these findings, determine clinical significance, and elucidate potential mechanisms underlying these associations.

New guidelines for research in airway device evaluation: time for an updated approach (ADEPT-2) to the Difficult Airway Society's 'ADEPT' strategy?

In this article we present the learning from a clinical study of airway device evaluation, conducted under the framework of the Difficult Airway Society (DAS, UK) 'ADEPT' (airway device evaluation project team) strategy. We recommend a change in emphasis from small scale randomised controlled trials conducted as research, to larger-scale observational, post-marketing evaluation audits as a way of obtaining more meaningful information.

Impact of Fluoride on Associations between Free Sugars Intake and Dental Caries in US Children.

OBJECTIVE: Dental caries is the most prevalent chronic disease in US children, with the highest burden among Black and Hispanic youth. Sugars are a primary risk factor, but few studies have specifically measured intakes of free sugars and related this to dental caries or explored the extent to which water fluoride mitigates the cariogenicity of free sugars. Furthermore, the cariogenicity of certain free sugars sources, such as extruded fruit and vegetable products, is unclear. METHODS: Using cross-sectional data on 4,906 children aged 2 to 19 y in the US National Health and Nutrition Examination Survey 2013-2016, we examined associations of free sugars intake with counts of decayed or filled primary tooth surfaces (dfs) and decayed, missing, or filled permanent surfaces (DMFS) in negative binomial regressions. Stratified models examined these associations in children with home water fluoride above or below the Centers for Disease Control and Prevention (CDC)-recommended level of 0.7 ppm. RESULTS: Free sugars accounted for 16.4% of energy, primarily contributed by added sugars. In adjusted models, a doubling in the percentage of energy from free sugars was associated with 22% (95% confidence interval [CI], 1%-47%) greater dfs among children aged 2 to 8. A doubling in energy from added sugars was associated with 20% (95% CI, 1%-42%) greater dfs and 10% (95% CI, 2%-20%) greater DMFS in children aged 6 to 19 y. Beverages were the most important source of added sugars associated with increased caries. Other free sugars were not associated with dfs or DMFS. Associations between free sugars and caries were diminished among children with home water fluoride of 0.7 ppm or greater. CONCLUSIONS: Free sugars intake, especially in the form of added sugars and specifically in sweetened beverages, was associated with higher dental caries. Water fluoride exposures modify these associations, reducing caries risk in the primary dentition of children whose home water meets recommended fluoride levels. KNOWLEDGE TRANSFER STATEMENT: Intake of free sugars, especially in the form of added sugars and specifically in beverages, was associated with higher dental caries in US children in this study. Water fluoride exposure at CDC-recommended levels protected against caries, especially in the primary dentition. These findings suggest that household water fluoridation at CDC-recommended levels protects against the cariogenic potential of free and added sugars during childhood.

Assessing a novel second generation laryngeal mask airway using the 'ADEPT' approach: results from the LMA® Protector™ observational study.

To address the problem of lack of clinical evidence for airway devices introduced to the market, the Difficult Airway Society (UK) developed an approach (termed ADEPT; Airway Device Evaluation Project Team) to standardise the model for device evaluation. Under this framework we assessed the LMA Protector, a second generation laryngeal mask airway. A total of 111 sequential adult patients were recruited and the LMA Protector inserted after induction of general anaesthesia. Effective insertion was confirmed by resistance to further distal movement, manual ventilation, and listening for gas leakage at the mouth. The breathing circuit was connected to the airway channel and airway patency confirmed with manual test ventilation at 20 cm H20 (water) pressure for 3 s. Data was collected in relation to the time for placement, intraoperative performance and postoperative performance of the airway device. Additionally, investigators rated the ease of insertion and adequacy of lung ventilation on a 5-point scale. The median (interquartile range [range]) time taken to insertion of the device was 31 (26-40[14-780]) s with the ability to ventilate after device insertion 100 (95% CI 96.7- 100)%. Secondary endpoints included one or more manoeuvres 60.3 (95% CI 50.6-69.5)% cases requiring to assist insertion; a median ease of insertion score of 4 (2-5[3-5]), and a median adequacy of ventilation score of 5 (5-5[4-5]). However, the first time insertion rate failure was 9.9% (95% CI 5.1-17.0%). There were no episodes of patient harm recorded, particularly desaturation. The LMA Protector appears suitable for clinical use, but an accompanying article discusses our reflections on the ADEPT approach to studying airway devices from a strategic perspective.

Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells.

Estrogen receptor alpha (ERα) is a ligand-dependent master transcriptional regulator and key driver of breast cancer pathology. Small molecule hormones and competitive antagonists favor unique ERα conformational ensembles that elicit ligand-specific transcriptional programs in breast cancer and other hormone-responsive tissues. By affecting disparate ligand binding domain structural features, unconventional ligand scaffolds can redirect ERα genomic binding patterns to engage novel therapeutic transcriptional programs. To improve our understanding of these ERα structure-transcriptional relationships, we develop a series of chemically unconventional antagonists based on the antiestrogens elacestrant and lasofoxifene. High-resolution x-ray co-crystal structures show that these molecules affect both classical and unique structural motifs within the ERα ligand binding pocket. They show moderately reduced antagonistic potencies on ERα genomic activities but are effective anti-proliferative agents in luminal breast cancer cells. Interestingly, they favor a 4-hydroxytamoxifen-like accumulation of ERα in breast cancer cells but lack uterotrophic activities in an endometrial cell line. Importantly, RNA sequencing shows that the lead molecules engage transcriptional pathways similar to the selective estrogen receptor degrader fulvestrant. This advance shows that fulvestrant-like genomic activities can be achieved without affecting ERα accumulation in breast cancer cells.

Translation, linguistic validation and reliability of FACT-H&N questionnaire in Oral Cancer patients in Sudan.

BACKGROUND: This study aimed to translate and validate an Arabic version of the Functional Assessment of Cancer Therapy Head and Neck Scale (FACT-H&N, v-4) for use among Sudanese oral cancer patients. METHODS: The instrument underwent translation and validation following the standard FACT translation methodology. The translated instrument was pre-tested for face validity and content validity using semi-structured, in-depth interviews with ten oral cancer patients to assess acceptability. The questionnaire was pilot tested with 60 patients; reliability was tested for internal consistency with Cronbach's alpha while construct validity was tested using 'known-group validity'. RESULTS: The pre-test study revealed no major issues, apart from a reluctance to answer questions on sexual satisfaction. The FACT-H&N demonstrated good internal consistency, it considered five particular constructs: PWB, SWB, EWB, FWB and FACT-H&N, their Cronbach's α values were positive and close to 1 with values of 0.85, 0.788, 0.86, 0.895 and 0.703 respectively, indicating that the questionnaire was valid and the responses consistent. Sixty patients were asked the global health-related quality of life item, 36.3% rated their QOL as very good or good (36.3%), while 41.7% rated it as average, and 21.7% as poor or very poor. Then FACT subscale mean scores were tabulated against three categories; patients with very poor/poor recorded significantly lower scores indicating construct validity. Some psychometric properties were consistent with other FACT-H&N translations such as the Chinese, French, Pakistani and Malaysian. CONCLUSIONS: This study validates the Arabic version of the FACT-H&N. It is a reliable tool and, will assist further QoL research in other Arabic-speaking countries.

While survival rates are routinely used to evaluate treatment outcomes in oral cancer, increased understanding of the human cost of this disease highlights the need to also consider the impact of the disease and therapy on patients' quality of life (QoL). Measurement of quality of life outcomes requires a validated QoL questionnaire with proven applicability in that specific context. Little research has been undertaken on the QoL of cancer patients in Sudan and no published research exists to date on the QoL of Sudanese oral cancer patients. While an Arabic version of the FACT-G general questionnaire exists, the FACT-H&N module was not previously available in Arabic. This paper describes the translation of the FACT-H&N from English into Arabic to suit Sudanese patients and other Arabic-speaking patients, with a detailed pre-test review by 10 patients, a pilot study with 60 patients and further validation with 130 patients. This study represents the first QoL research undertaken in oral cancer patients in Sudan and provides some insight into the impact of oral cancer on their lives. Findings from this study indicate that the Arabic version of the FACT-H&N questionnaire is a valid, reliable and acceptable method for assessing health related QoL in Arabic-speaking Sudanese oral cancer patients. This work will benefit future researchers working with Arabic-speaking oral cancer patients.

Preventing unrecognised oesophageal intubation: a consensus guideline from the Project for Universal Management of Airways and international airway societies.

Across multiple disciplines undertaking airway management globally, preventable episodes of unrecognised oesophageal intubation result in profound hypoxaemia, brain injury and death. These events occur in the hands of both inexperienced and experienced practitioners. Current evidence shows that unrecognised oesophageal intubation occurs sufficiently frequently to be a major concern and to merit a co-ordinated approach to address it. Harm from unrecognised oesophageal intubation is avoidable through reducing the rate of oesophageal intubation, combined with prompt detection and immediate action when it occurs. The detection of 'sustained exhaled carbon dioxide' using waveform capnography is the mainstay for excluding oesophageal placement of an intended tracheal tube. Tube removal should be the default response when sustained exhaled carbon dioxide cannot be detected. If default tube removal is considered dangerous, urgent exclusion of oesophageal intubation using valid alternative techniques is indicated, in parallel with evaluation of other causes of inability to detect carbon dioxide. The tube should be removed if timely restoration of sustained exhaled carbon dioxide cannot be achieved. In addition to technical interventions, strategies are required to address cognitive biases and the deterioration of individual and team performance in stressful situations, to which all practitioners are vulnerable. These guidelines provide recommendations for preventing unrecognised oesophageal intubation that are relevant to all airway practitioners independent of geography, clinical location, discipline or patient type.

Building bridges between natural and social science disciplines: a standardized methodology to combine data on ecosystem quality trends.

Despite a growing interest in interdisciplinary research, systematic ways of how to integrate data from different disciplines are still scarce. We argue that successful resource management relies on two key data sources: natural science data, which represents ecosystem structure and processes, and social science data, which describes people's perceptions and understanding. Both are vital, mutually complementing information sources that can underpin the development of feasible and effective policies and management interventions. To harvest the added value of combined knowledge, a uniform scaling system is needed. In this paper, we propose a standardized methodology to connect and explore different types of quantitative data from the natural and social sciences reflecting temporal trends in ecosystem quality. We demonstrate this methodology with different types of data such as fisheries stocks and mangrove cover on the one hand and community's perceptions on the other. The example data are collected from three United Nations Educational Scientific and Cultural Organization (UNESCO) Biosphere reserves and one marine park in Southeast Asia. To easily identify patterns of convergence or divergence among the datasets, we propose heat maps using colour codes and icons for language- and education-independent understandability. Finally, we discuss the limitations as well as potential implications for resource management and the accompanying communication strategies. This article is part of the theme issue 'Nurturing resilient marine ecosystems'.

Adolescent Binge Drinking Is Associated With Accelerated Decline of Gray Matter Volume.

The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan-Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results of this study highlight the negative effects of binge drinking on the developing brain. Our results present novel findings that cortical GMV decreases were greater in closer proximity to binge drinking episodes in a dose-response manner. This relation suggests a causal effect and raises the possibility that normal growth trajectories may be reinstated with alcohol abstinence.

Trajectories of brain development reveal times of risk and factors promoting resilience to alcohol use during adolescence.

Alcohol use disorder (AUD) is recognized as harmful for the developing brain. Numerous studies have sought environmental and genetic risk factors that predict the development of AUD, but recently identified resilience factors have emerged as protective. This chapter reviews normal processes of brain development in adolescence and emerging adulthood, delineates disturbed growth neurotrajectories related to heavy drinking, and identifies potential endogenous, experiential, and time-linked brain markers of resilience. For example, concurrent high dorsolateral prefrontal activation serving inhibitory control and low nucleus accumbens activation serving reward functions engender positive adaptation and low alcohol use. Also discussed is the role that moderating factors have in promoting risk for or resilience to AUD. Longitudinal research on the effects of all levels of alcohol drinking on the developing brain remains crucial and should be pursued in the context of resilience, which is a promising direction for identifying protective biomarkers against developing AUDs.

Diabetes care and pregnancy outcomes for women with pregestational diabetes in Ireland.

AIMS: Pre-gestational diabetes mellitus (PGDM) is associated with adverse outcomes. We aimed to examine pregnancies affected by PGDM; report on these pregnancy outcomes and compare outcomes for patients with type 1 versus type 2 diabetes mellitus; compare our findings to published Irish and United Kingdom (UK) data and identify potential areas for improvement. METHODS: Between 2016 and 2018 information on 679 pregnancies from 415 women with type 1 Diabetes Mellitus and 244 women with type 2 diabetes was analysed. Data was collected on maternal characteristics; pregnancy preparation; glycaemic control; pregnancy related complications; foetal and maternal outcomes; unscheduled hospitalisations; congenital anomalies and perinatal deaths. RESULTS: Only 15.9% of women were adequately prepared for pregnancy. Significant deficits were identified in availability and attendance at pre-pregnancy clinic, use of folic acid, attaining appropriate glycaemic targets and appropriate retinal screening. The majority of pregnancies (n = 567, 83.5%) resulted in a live birth but the large number of infants born large for gestational age (LGA) (n = 280, 49.4%), born prematurely <37 weeks and requiring neonatal intensive care unit (NICU) admission continue to be significant issues. CONCLUSIONS: This retrospective cohort study identifies multiple targets for improvements in the provision of care to women with pre-gestational DM which are likely to translate into better pregnancy outcomes.

Airway management guidance for the endemic phase of COVID-19.

It is now apparent that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) will remain endemic for some time. Improved therapeutics and a vaccine may shorten this period, but both are far from certain. Plans must be put in place on the assumption that the virus and its disease will continue to affect the care of patients and the safety of staff. This will impact particularly on airway management due to the inherent risk to staff during such procedures. Research is needed to clarify the nature and risk of respiratory aerosol-generating procedures. Improved knowledge of the dynamics of SARS-CoV-2 infection and immunity is also required. In the meantime, we describe the current status of airway management during the endemic phase of the COVID-19 pandemic. Some controversies remain unresolved, but the safety of patients and staff remains paramount. Current evidence does not support or necessitate dramatic changes to choices for anaesthetic airway management. Theatre efficiency and training issues are a challenge that must be addressed, and new information may enable this.