Sleep-disordered breathing and comorbidities: Role of the upper airway and craniofacial skeleton

Obstructive sleep-disordered breathing (SDB), which includes primary snoring through to obstructive sleep apnea syndrome (OSAS), may cause compromise of respiratory gas exchange during sleep, related to transient upper airway narrowing disrupting ventilation, and causing oxyhemoglobin desaturation and poor sleep quality. SDB is common in chronic disorders and has significant implications for health. With prevalence rates globally increas-ing, this condition is causing a substantial burden on health care costs. Certain populations, including people with sickle cell disease (SCD), exhibit a greater prevalence of OSAS. A review of the literature provides the available normal polysomnography and oximetry data for reference and documents the structural upper airway differences between those with and without OSAS, as well as between ethnicities and disease states. There may be differences in craniofacial development due to atypical growth trajectories or extramedullary hematopoiesis in anemias such as SCD. Studies involving MRI of the upper airway illustrated that OSAS populations tend to have a greater amount of lymphoid tissue, smaller airways, and smaller lower facial skeletons from measurements of the mandible and linear mental spine to clivus. Understanding the potential relationship between these anatomical landmarks and OSAS could help to stratify treatments, guiding choice towards those which most effectively resolve the obstruction. OSAS is relatively common in SCD populations, with hypoxia as a key manifestation, and sequelae including increased risk of stroke. Combatting any structural defects with appropriate interventions could reduce hypoxic exposure and consequently reduce the risk of comorbidities in those with SDB, warranting early treatment interventions

Polarimetric airborne scientific instrument, mark 2, an ice‐sounding airborne synthetic aperture radar for subglacial 3D imagery

Polarimetric Airborne Scientific INstrument, mark 2 (PASIN2) is a 150 MHz coherent pulsed radar with the purpose of deep ice sounding for bedrock, subglacial channels and ice‐water interface detection in Antarctica. It is designed and operated by the British Antarctic Survey from 2014. With multiple antennas, oriented along and across‐track, for transmission and reception, it enables polarimetric 3D estimation of the ice base with a single pass, reducing the gridding density of the survey paths. The off‐line data processing stream consists of channel calibration; 2D synthetic aperture radar (SAR) imaging based on back‐projection, for along‐track and range dimensions; and finally, a direction of arrival estimation (DoA) of the remaining across‐track angle, by modifying the non‐linear MUSIC algorithm. Calibration flights, during the Antarctic Summer campaigns in 16/17 and 19/20 seasons, assessed and validated the instrument and processing performances. Imaging flights over ice streams and ice shelves close to grounding lines demonstrate the 3D sensing capabilities. By resolving directional ambiguities and accounting for reflector across‐track location, the true ice thickness and bed elevation are obtained, thereby removing the error of the usual assumption of vertical DoA, that greatly influence the output of flow models of ice dynamics

Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

A latent trait look at pretest-posttest validation of criterion-referenced test items

Since Cox and Vargas (1966) introduced their pretest-posttest validity index for criterion-referenced test items, a great number of additions and modifications have followed. All are based on the idea of gain scoring; that is, they are computed from the differences between proportions of pretest and posttest item responses. Although the method is simple and generally considered as the prototype of criterion-referenced item analysis, it has many and serious disadvantages. Some of these go back to the fact that it leads to indices based on a dual test administration- and population-dependent item p values. Others have to do with the global information about the discriminating power that these indices provide, the implicit weighting they suppose, and the meaningless maximization of posttest scores they lead to. Analyzing the pretest-posttest method from a latent trait point of view, it is proposed to replace indices like Cox and Vargas’ Dpp by an evaluation of the item information function for the mastery score. An empirical study was conducted to compare the differences in item selection between both methods

Health and life insurance as an alternative to malpractice tort law

<p>Abstract</p> <p>Background</p> <p>Tort law has legitimate social purposes of deterrence, punishment and compensation, but medical tort law does none of these well. Tort law could be counterproductive in medicine, encouraging costly defensive practices that harm some patients, restricting access to care in some settings and discouraging innovation.</p> <p>Discussion</p> <p>Patients might be better served by purchasing combined health and life insurance policies and waiving their right to pursue malpractice claims. The combined policy should encourage the insurer to profit by inexpensively delaying policyholders' deaths. A health and life insurer would attempt to minimize mortal risks to policyholders from any cause, including medical mistakes and could therefore pursue systematic quality improvement efforts. If policyholders trust the insurer to seek, develop and reward genuinely effective care; identify, deter and remediate poor care; and compensate survivors through the no-fault process of paying life insurance benefits, then tort law is largely redundant and the right to sue may be waived. If expensive defensive medicine can be avoided, that savings alone could pay for fairly large life insurance policies.</p> <p>Summary</p> <p>Insurers are maligned largely because of their logical response to incentives that are misaligned with the interests of patients and physicians in the United States. Patient, provider and insurer incentives could be realigned by combining health and life insurance, allowing the insurer to use its considerable information access and analytic power to improve patient care. This arrangement would address the social goals of malpractice torts, so that policyholders could rationally waive their right to sue.</p

How I report breast magnetic resonance imaging studies for breast cancer staging and screening

Magnetic resonance imaging (MRI) of the breast is the most sensitive imaging technique for the diagnosis and local staging of primary breast cancer and yet, despite the fact that it has been in use for 20 years, there is little evidence that its widespread uncritical adoption has had a positive impact on patient-related outcomes. This has been attributed previously to the low specificity that might be expected with such a sensitive modality, but with modern techniques and protocols, the specificity and positive predictive value for malignancy can exceed that of breast ultrasound and mammography. A more likely explanation is that historically, clinicians have acted on MRI findings and altered surgical plans without prior histological confirmation. Furthermore, modern adjuvant therapy for breast cancer has improved so much that it has become a very tall order to show a an improvement in outcomes such as local recurrence rates. In order to obtain clinically useful information, it is necessary to understand the strengths and weaknesses of the technique and the physiological processes reflected in breast MRI. An appropriate indication for the scan, proper patient preparation and good scan technique, with rigorous quality assurance, are all essential prerequisites for a diagnostically relevant study. The use of recognised descriptors from a standardised lexicon is helpful, since assessment can then dictate subsequent recommendations for management, as in the American College of Radiology BI-RADS (Breast Imaging Reporting and Data System) lexicon (Morris et al., ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System, 2013). It also enables audit of the service. However, perhaps the most critical factor in the generation of a meaningful report is for the reporting radiologist to have a thorough understanding of the clinical question and of the findings that will influence management. This has never been more important than at present, when we are in the throes of a remarkable paradigm shift in the treatment of both early stage and locally advanced breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40644-016-0078-0) contains supplementary material, which is available to authorized users

Chromosomal aberrations and aneuploidy in oral potentially malignant lesions: distinctive features for tongue

<p>Abstract</p> <p>Background</p> <p>The mucosae of the oral cavity are different at the histological level but appear all equally exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia may develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs) in the OPMLs from different oral anatomical subsites.</p> <p>Methods</p> <p>Samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on DNA obtained from diploid nuclei suspensions directly. When aneuploid nuclei were detected, these were physically separated from diploid nuclei on the base of their DI values by means of a DNA-FCM-Sorter in order to improve the a-CGH analysis.</p> <p>Results</p> <p>Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites.</p> <p>Conclusions</p> <p>We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this hypothesis should be validated in a prospective clinical study.</p

A SRY-HMG box frame shift mutation inherited from a mosaic father with a mild form of testicular dysgenesis syndrome in Turner syndrome patient

Background: Sex determining factor (SRY) located on the short arm of the Y chromosome, plays an important role in initiating male sex determination, resulting in development of testicular tissue. Presence of the SRY gene in females results in XY sex reversal and increased risk of gonadal germ cell tumours if the karyotype also includes the so-called GonadoBlastoma on the Y chromosome (GBY) region. The majority of mutations within the SRY gene are de novo affecting only a single individual in the family. The mutations within the high-mobility group (HMG) region have the potential to affect its DNA binding activity.Case Presentation: We performed G- and R-banding cytogenetic analysis of the patient and her family members including her father. We also performed molecular genetic analysis of SRY gene. Cytogenetic analysis in the patient (Turner Syndrome) revealed the mosaic karyotype as 45, X/46, XY (79%/21% respectively) while her father (milder features with testicular dysgenesis syndrome) has a normal male karyotype (46, XY). Using molecular approach, we screened the patient and her father for mutations in the SRY gene. Both patient and her father showed the same deletion of cytosine within HMG box resulting in frame shift mutation (L94fsX180), the father in a mosaic pattern. Histological examination of the gonads from the patient revealed the presence of gonadoblastoma formation, while the father presented with oligoasthenozoospermia and a testicular seminoma. The frameshift mutation at this codon is novel, and may result in a mutated SRY protein.Conclusion: Our results suggest that lack of a second sex chromosome in majority cells of the patient may have triggered the short stature and primary infertility, and the mutated SRY protein may be associated with the development of gonadoblastoma. It is of importance to note that mosaic patients without a SRY mutation also have a risk for malignant germ cell tumors

Awareness, Accuracy, and Predictive Validity of Self-Reported Cholesterol in Women

BACKGROUND: Although current guidelines emphasize the importance of cholesterol knowledge, little is known about accuracy of this knowledge, factors affecting accuracy, and the relationship of self-reported cholesterol with cardiovascular disease (CVD). METHODS: The 39,876 female health professionals with no prior CVD in the Women’s Health Study were asked to provide self-reported and measured levels of total and high-density lipoprotein (HDL) cholesterol. Demographic and cardiovascular risk factors were considered as determinants of awareness and accuracy. Accuracy was evaluated by the difference between reported and measured cholesterol. In addition, we examined the relationship of self-reported cholesterol with incident CVD over 10 years. RESULTS: Compared with women who were unaware of their cholesterol levels, aware women (84%) had higher levels of income, education, and exercise and were more likely to be married, normal in weight, treated for hypertension and hypercholesterolemia, nonsmokers, moderate drinkers, and users of hormone therapy. Women underestimated their total cholesterol by 9.7 mg/dL (95% CI: 9.2–10.2); covariates explained little of this difference (R(2) < .01). Higher levels of self-reported cholesterol were strongly associated with increased risk of CVD, which occurred in 741 women (hazard ratio 1.23/40 mg/dL cholesterol, 95% CI: 1.15–1.33). Women with elevated cholesterol who were unaware of their level had particularly increased risk (HR=1.88, P <. 001) relative to aware women with normal measured cholesterol. CONCLUSION: Women with obesity, smoking, untreated hypertension, or sedentary lifestyle have decreased awareness of their cholesterol levels. Self-reported cholesterol underestimates measured values, but is strongly related to CVD. Lack of awareness of elevated cholesterol is associated with increased risk of CVD

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques