Development of a leakage impact assessment for patients with a stoma, who may be impacted by leakage.

For people living with a stoma leakage is unpredictable. Despite advances in stoma products, leakage can lead to soiling and this, along with worrying about leakage, can significantly affect patients' everyday lives and impact their quality of life. It is also associated with excessive product use and increased healthcare resources. Leakage therefore remains a major unmet need for many people living with a stoma. To address this, Coloplast Ltd in collaboration with the authors and a broader group of stoma care nurses have worked together to develop a first version of the Leakage Impact Assessment. This assessment is intended to identify patients who struggle with leakage and leakage worry, and who might benefit from the reassurance that a new digital leakage notification system, Heylo™, can provide. This article reviews the evidence for leakage and its impact on people living with a stoma and outlines the development process for the assessment.

Medications for daytime sleepiness in individuals with idiopathic hypersomnia.

BACKGROUND: Idiopathic hypersomnia is a disorder of excessive daytime sleepiness, often accompanied by long sleep times or pronounced difficulty in awakening, in the absence of a known cause. The optimal treatment strategy for idiopathic hypersomnia is currently unknown. OBJECTIVES: To assess the effects of medications for daytime sleepiness and related symptoms in individuals with idiopathic hypersomnia and, in particular, whether medications may: 1. reduce subjective measures of sleepiness; 2. reduce objective measures of sleepiness; 3. reduce symptoms of cognitive dysfunction; 4. improve quality of life; and 5. be associated with adverse events. SEARCH METHODS: We searched the following databases on 4 February 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 1 February 2021), and reference lists of articles. CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialized registers of Cochrane Review Groups, including the Cochrane Epilepsy Group. We previously searched the WHO ICTRP separately when loading of ICTRP records into CRS Web was temporarily suspended. SELECTION CRITERIA: Randomized studies comparing any medication to placebo, another medication, or a behavioral intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional data. We collected data on adverse events from the included trials. MAIN RESULTS: We included three trials, with a total of 112 participants. Risk of bias was low for the included studies. Two pharmaceutical company-sponsored trials compared modafinil with placebo, involving 102 participants, nearly all of whom had idiopathic hypersomnia without long sleep time. Modafinil significantly improved self-reported sleepiness on the Epworth Sleepiness Scale by 5.08 points more than placebo (95% confidence interval (CI) 3.01 to 7.16; 2 studies, 101 participants; high-certainty evidence). Modafinil also significantly improved disease severity on the Clinical Global Impression of Severity scale by 1.02 points (95% CI 0.11 to 1.93; 1 study, 30 participants; moderate-certainty evidence) and resulted in a greater proportion of participants who were "much improved" or "very much improved" on the Clinical Global Impression of Change (odds ratio (OR) for improvement 5.14, 95% CI 1.76 to 15.00; 1 study, 70 participants; moderate-certainty evidence). Ability to remain awake on the Maintenance of Wakefulness Test was significantly improved with modafinil, by 4.74 minutes more than with placebo (95% CI 2.46 to 7.01; 2 studies, 99 participants; high-certainty evidence). Ratings of exhaustion and effectiveness/performance were improved with modafinil compared to placebo in one study. Number of naps per week was no different between modafinil and placebo across two studies. Participants receiving modafinil experienced more side effects, although the difference did not reach statistical significance (OR 1.68, 95% CI 0.28 to 9.94; 2 studies, 102 participants; low-certainty evidence). One trial studying 20 participants with different disorders of sleepiness included 10 participants with idiopathic hypersomnia, with or without long sleep time, and compared clarithromycin to placebo. We only included the subset of trial data for those participants with idiopathic hypersomnia, per our protocol. There were no significant differences between clarithromycin and placebo for the Epworth Sleepiness Scale, psychomotor vigilance testing, sleep inertia, other subjective ratings, or side effects. AUTHORS' CONCLUSIONS: Modafinil is effective for the treatment of several aspects of idiopathic hypersomnia symptomatology, based on studies predominantly including participants with idiopathic hypersomnia without long sleep times, with low risk of bias, and evidence certainty ranging from high to low. There is insufficient evidence to conclude whether clarithromycin is effective for the treatment of idiopathic hypersomnia. There is a clear need for additional studies testing interventions for the treatment of idiopathic hypersomnia.

Consequences of Depletion of Susceptibles for Hazard Ratio Estimators Based on Propensity Scores.

We use simulated data to examine the consequences of depletion of susceptibles for hazard ratio (HR) estimators based on a propensity score (PS). First, we show that the depletion of susceptibles attenuates marginal HRs toward the null by amounts that increase with the incidence of the outcome, the variance of susceptibility, and the impact of susceptibility on the outcome. If susceptibility is binary then the Bross bias multiplier, originally intended to quantify bias in a risk ratio from a binary confounder, also quantifies the ratio of the instantaneous marginal HR to the conditional HR as susceptibles are depleted differentially. Second, we show how HR estimates that are conditioned on a PS tend to be between the true conditional and marginal HRs, closer to the conditional HR if treatment status is strongly associated with susceptibility and closer to the marginal HR if treatment status is weakly associated with susceptibility. We show that associations of susceptibility with the PS matter to the marginal HR in the treated (ATT) though not to the marginal HR in the entire cohort (ATE). Third, we show how the PS can be updated periodically to reduce depletion-of-susceptibles bias in conditional estimators. Although marginal estimators can hit their ATE or ATT targets consistently without updating the PS, we show how their targets themselves can be misleading as they are attenuated toward the null. Finally, we discuss implications for the interpretation of HRs and their relevance to underlying scientific and clinical questions. See video Abstract: http://links.lww.com/EDE/B727.

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

OBJECTIVE: To update the 2002 version of "Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient." DESIGN: A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. METHODS: Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. RESULTS: The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death.

Turning hepatitis C into a real virus.

The reality of hepatitis C is inescapable for the estimated 130 million people worldwide chronically infected with the virus. Yet this pathogen has been notoriously difficult to move from the infected individual into experimental systems, and each advance--from the identification of the infectious agent to its culture and study--has been a significant challenge. As a result of unrelenting technical hurdles, preventative and therapeutic options have been slow to reach hepatitis C patients. More than 35 years since the recognition of the disease, there is no vaccine available, and the only approved treatment, a combination of pegylated interferon-alpha (IFN-α) and ribavirin, is frequently ineffective. Decades of research, however, have resulted in systematic progress and much is now known about this once elusive pathogen. Most importantly, key breakthroughs have stimulated drug discovery, and the first generation of specifically targeted antiviral inhibitors is poised to enter the market. This review provides a look back at progress in developing tractable model systems for this important agent of chronic hepatitis.

Evaluation of T1-Weighted MRI to Detect Intratumoral Hemorrhage Within Papillary Renal Cell Carcinoma as a Feature Differentiating From Angiomyolipoma Without Visible Fat.

OBJECTIVE: The objective of the present study is to determine whether hemorrhage within papillary renal cell carcinoma (RCC) can be detected using T1-weighted MRI and to ascertain whether it can be used to differentiate papillary RCC from angiomyolipoma (AML) without visible fat. MATERIALS AND METHODS: A retrospective case-control study compared 11 AMLs without visible fat with 58 papillary RCCs smaller than 5 cm that were evaluated using MRI between 2003 and 2015. Two blinded radiologists subjectively evaluated MR images to identify the presence of intratumoral hemorrhage on the basis of a decrease in signal intensity (SI) on in-phase, compared with opposed-phase, chemical-shift MRI and also on the basis of the SI of the lesion compared with that of the renal cortex on fat-suppressed T1-weighted MRI. A third radiologist established consensus and measured the ratio of the SI of the lesion to that of the renal cortex (hereafter referred to as the "SI ratio") on T2-weighted MRI; the SI loss index, as calculated using the equation [(SItumorIP - SItumorOP) / SItumorOP] × 100, where IP denotes the in-phase image and OP denotes the opposed-phase image; and the SI ratio on fat-suppressed T1-weighted MRI. Analyses were performed using tests of association and ROCs. RESULTS: When AMLs without visible fat were compared with papillary RCCs, no statistically significant difference in the T2-weighted SI ratio was noted (p = 0.08). Papillary RCCs had a lower mean (± SD) SI loss index (-3.7% ± 17.3%; range, -51.3% to 31.3%) than did AMLs without visible fat (37.8% ± 76.1%; range, -15.6% to 184.4%) (p < 0.001). A mean SI loss index of less than -16% resulted in an AUC of 0.71 (95% CI, 0.52-0.91), with a sensitivity and specificity of 22.8% and 100%, respectively, for the diagnosis of papillary RCC. After consensus review, none of the AMLs without visible fat and 16 of the 58 papillary RCCs (27.6%) were found to have a decrease in SI on subjective analysis (p = 0.06, κ = 0.60). Between groups, no differences were noted in the SI ratio on fat-suppressed T1-weighted MRI (p = 0.58) or in the SI observed on subjective analysis of fat-suppressed T1-weighted MRI (p = 0.20, κ = 0.48). CONCLUSION: The presence of intratumoral hemorrhage within papillary RCC is a specific feature that differentiates papillary RCCs from AMLs without visible fat. Subjective analysis may be more clinically appropriate than chemical-shift MRI because of limitations in the quantitative measurement of T2* signal with the use of chemical-shift MRI.

Proton spectroscopic imaging of brain metabolites in basal ganglia of healthy older adults.

OBJECT: We sought to measure brain metabolite levels in healthy older people. MATERIALS AND METHODS: Spectroscopic imaging at the level of the basal ganglia was applied in 40 participants aged 73-74 years. Levels of the metabolites N-acetyl aspartate (NAA), choline, and creatine were determined in "institutional units" (IU) corrected for T1 and T2 relaxation effects. Structural imaging enabled determination of grey matter (GM), white matter (WM), and cerebrospinal fluid content. ANOVA analysis was carried out for voxels satisfying quality criteria. RESULTS: Creatine levels were greater in GM than WM (57 vs. 44 IU, p < 0.001), whereas choline and NAA levels were greater in WM than GM [13 vs. 10 IU (p < 0.001) and 76 versus 70 IU (p = 0.03), respectively]. The ratio of NAA/cre was greater in WM than GM (2.1 vs. 1.4, p = 0.001) as was that of cho/cre (0.32 vs. 0.16, p < 0.001). A low voxel yield was due to brain atrophy and the difficulties of shimming over an extended region of brain. CONCLUSION: This study addresses the current lack of information on brain metabolite levels in older adults. The normal features of ageing result in a substantial loss of reliable voxels and should be taken into account when planning studies. Improvements in shimming are also required before the methods can be applied more widely.

Potential effect of skull thickening on the associations between cognition and brain atrophy in ageing.

BACKGROUND: intracranial volume (ICV) is commonly used as a marker of premorbid brain size in neuroimaging studies as it is thought to remain fixed throughout adulthood. However, inner skull table thickening would encroach on ICV and could mask actual brain atrophy. OBJECTIVE: we investigated the effect that thickening might have on the associations between brain atrophy and cognition. METHODS: the sample comprised 57 non-demented older adults who underwent structural brain MRI at mean age 72.7 ± 0.7 years and were assessed on cognitive ability at mean age 11 and 73 years. Principal component analysis was used to derive factors of general cognitive ability (g), information processing speed and memory from the recorded cognitive ability data. The total brain tissue volume and ICV with (estimated original ICV) and without (current ICV) adjusting for the effects of inner table skull thickening were measured. General linear modelling was used to test for associations. RESULTS: all cognitive ability variables were significantly (P < 0.01) associated with percentage total brain volume in ICV measured without adjusting for skull thickening (g: η(2) = 0.177, speed: η(2) = 0.264 and memory: η(2) = 0.132). After accounting for skull thickening, only speed was significantly associated with percentage total brain volume in ICV (η(2) = 0.085, P = 0.034), not g or memory. CONCLUSIONS: not accounting for skull thickening when computing ICV can distort the association between brain atrophy and cognitive ability in old age. Larger samples are required to determine the true effect.

The total artificial heart: where have we been, where are we now, where are we going?

The incidence and prevalence of end-stage heart failure continue to rise; however, the number of donor hearts available for transplantation continues to be limited. Therefore, alternatives to transplantation, such as the use of total artificial hearts (TAH), are necessary. The long and winding road to the development and implantation of the ideal TAH remains under construction. Although efforts have been ongoing for almost a century, researchers and clinicians continue to improve currently available TAHs and design and construct new models. With mortality and morbidity rates decreasing, particularly at high-volume centers with a dedicated team and carefully selected patients, the use of TAHs as a bridge to transplantation, and even destination therapy in clinical trials, the future of TAHs is bright.

Heart Transplant Outcomes After Total Artificial Heart.

BACKGROUND: We sought to compare heart transplant (HTX) outcomes from patients with a total artificial heart (TAH), biventricular assist device (BiVAD), or left ventricular assist device (LVAD) as a bridge to transplant (BTT). Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)-Scientific Registry of Transplant Recipients (SRTR) created a dataset with TAH or durable mechanical circulatory support (MCS) who reached HTX between 2006 and 2015. METHODS: The retrospective analysis compared TAH outcomes with those with a BiVAD or LVAD before HTX. The primary outcome was posttransplant survival at 1, 36, and 60 months. Secondary outcomes included simultaneous heart-kidney transplants, donor characteristics, and mortality risk factors. INTERMACS-SRTR cohort had, at the time of HTX, 2762 patients with LVAD; 205 BiVAD (139 durable and 66 temporary RVAD); 176 TAH (6 prior HeartMate II). RESULTS: Sixty months after HTX, mortality rates were 16.5% in the total group: LVAD 15.2%, BiVAD 22.4%, and TAH 29%. Survival differed between the LVAD, the TAH, and BiVAD but not between the BiVAD and TAH groups. One-year survival and complication rates were similar across groups-there was no difference in survival by donor age in the overall cohort. There was a difference in TTD based on recipient age in the LVAD group but not in BiVAD or TAH groups. Occurrence of HTX-kidney and post-transplant dialysis were higher in the TAH versus LVAD and BiVAD groups. CONCLUSIONS: The TAH is an efficacious BTT. Refinements in technology and patient selection may improve outcomes.

The Long-Term Care Data Cooperative: The Next Generation of Data Integration.

Despite important advances in the linkage of residents' Medicare claims and Minimum Data Set (MDS) information, the data infrastructure for long-term care remains inadequate for public health surveillance and clinical research. It is widely known that the evidence base supporting treatment decisions for older nursing home residents is scant as residents are systematically excluded from clinical trials. Electronic health records (EHRs) hold the promise to improve this population's representation in clinical research, especially with the more timely and detailed clinical information available in EHRs that are lacking in claims and MDS. The COVID-19 pandemic shined a spotlight on the data gap in nursing homes. To address this need, the National Institute on Aging funded the Long-Term Care (LTC) Data Cooperative, a collaboration among providers and stakeholders in academia, government, and the private sector. The LTC Data Cooperative assembles residents' EHRs from major specialty vendors and facilitates linkage of these data with Medicare claims to create a comprehensive, longitudinal patient record. These data serve 4 key purposes: (1) health care operations and population health analytics; (2) public health surveillance; (3) observational, comparative effectiveness research; and (4) clinical research studies, including provider and patient recruitment into Phase 3 and Phase 4 randomized trials. Federally funded researchers wanting to conduct pragmatic trials can now enroll their partnering sites in this Cooperative to more easily access the clinical data needed to close the evidence gaps in LTC. Linkage to Medicare data facilitates tracking patients' long-term outcomes after being discharged back to the community. As of August 2022, nearly 1000 nursing homes have joined, feedback reports to facilities are being piloted, algorithms for identifying infections are being tested, and proposals for use of the data have been reviewed and approved. This emerging EHR system is a substantial innovation in the richness and timeliness of the data infrastructure of the nursing home population.

A general factor of brain white matter integrity predicts information processing speed in healthy older people.

Human white matter integrity has been related to information processing speed, but it is unknown whether impaired integrity results from localized processes or is a general property shared across white matter tracts. Based on diffusion MRI scans of 132 healthy individuals with a narrow age range around 72 years, the integrity of eight major white matter tracts was quantified using probabilistic neighborhood tractography. Principal component analyses (PCAs) were conducted on the correlations between the eight tracts, separately for four tract-averaged integrity parameters: fractional anisotropy, mean diffusivity, and radial and axial diffusivity. For all four parameters, the PCAs revealed a single general factor explaining approximately 45% of the individual differences across all eight tracts. Individuals' scores on a general factor that captures the common variance in white matter integrity had significant associations with a general factor of information processing speed for fractional anisotropy (r = -0.24, p = 0.007) and radial diffusivity (r = 0.21, p = 0.016), but not with general intelligence or memory factors. Individual tracts showed no associations beyond what the common integrity factor explained. Just as different types of cognitive ability tests share much of their variance, these novel findings show that a substantial amount of variance in white matter integrity is shared between different tracts. Therefore, impaired cortical connection is substantially a global process affecting various major tracts simultaneously. Further studies should investigate whether these findings relate more to the role of tract integrity and information processing speed in nonpathological cognitive aging or in lifelong-stable processes.

Genetic analysis of the carboxy-terminal region of the hepatitis C virus core protein.

Hepatitis C virus (HCV) is a liver-tropic pathogen with severe health consequences for infected individuals. Chronic HCV infection can progress to cirrhosis and hepatocellular carcinoma and is a leading indicator for liver transplantation. The HCV core protein is an essential component of the infectious virus particle, but many aspects of its role remain undefined. The C-terminal region of the core protein acts as a signal sequence for the E1 glycoprotein and undergoes dual processing events during infectious virus assembly. The exact C terminus of the mature, virion-associated core protein is not known. Here, we performed genetic analyses to map the essential determinants of the HCV core C-terminal region, as well as to define the minimal length of the protein that can function for infectious virus production in trans.

Architects of assembly: roles of Flaviviridae non-structural proteins in virion morphogenesis.

Viruses of the Flaviviridae family, including hepatitis C, dengue and bovine viral diarrhoea, are responsible for considerable morbidity and mortality worldwide. Recent advances in our understanding of virion assembly have uncovered commonalities among distantly related members of this family. We discuss the emerging hypothesis that physical virion components are not alone in forming the infectious particle, but that non-structural proteins are intimately involved in orchestrating morphogenesis. Pinpointing the roles of Flaviviridae proteins in virion production could reveal new avenues for antiviral therapeutics.

Reliability of two techniques for assessing cerebral iron deposits with structural magnetic resonance imaging.

PURPOSE: To test the reliability of two computational methods for segmenting cerebral iron deposits (IDs) in the aging brain, given that its measurement in magnetic resonance imaging (MRI) is challenging due to the similar effect produced by other minerals, especially calcium, on T2*-weighted sequences. MATERIALS AND METHODS: T1-, T2*-weighted, and fluid-attenuated inversion recovery (FLAIR) MR brain images obtained at 1.5T from 70 subjects in their early 70s who displayed a wide range of brain IDs were analyzed. The first segmentation method used a multispectral approach based on the fusion of two or more structural sequences registered and mapped in the red/green color space followed by Minimum Variance Quantization. The second method employed a combined thresholding, size and shape analysis using T2*-weighted images augmented with visual information from T1-weighted data. RESULTS: Both segmentation techniques had high intra- and interobserver agreement (95% confidence interval [CI] = ± 57 voxels in a range from 0 to 1800), which decreased in subjects with significant microbleeds and/or IDs. However, the thresholding method was more observer dependent in identifying microbleeds and IDs boundaries than the multispectral approach. CONCLUSION: Both techniques proved to be in agreement and have good intra- and interobserver reliability. However, they have limitations, specifically with regard to automation and observer independence, so further work is required to develop fully user-independent methods of identifying cerebral IDs.

Which aspects of subjectively reported quality of life are important in predicting mortality beyond known risk factors? The Lothian Birth Cohort 1921 Study.

PURPOSE: To investigate which aspects of Quality of Life (QoL) (physical health, psychological, social-relationships, and environment) are important in predicting mortality. METHODS: A sample of 448 (194 men and 254 women) relatively healthy older adults reported their QoL using the WHOQOL-BREF. After a 9-year follow-up, survival analysis was carried out using Cox's proportional hazards regression. RESULTS: Only the General Health item (HR = 0.75, 95% CI: 0.64-0.89) and Physical Health Domain mean score (HR = 0.90, 95% CI: 86-0.95) significantly predicted mortality when controlling for age and sex. The single-item General Health measure was the stronger predictor of mortality and remained significant after socio-demographic, psychological (personality and cognition), health behaviour and health status measures were controlled for independently. When all measures were simultaneously controlled for, none of the items or domains on the WHOQOL-BREF significantly predicted mortality. CONCLUSION: Items addressing health-related QoL are the most important when predicting mortality. The findings support research demonstrating that subjectively rated, single-item general health questions accurately predict survival over and above socio-demographic, psychological, health behaviour and health status measures.

White matter integrity in the splenium of the corpus callosum is related to successful cognitive aging and partly mediates the protective effect of an ancestral polymorphism in ADRB2.

It has recently been reported that the evolutionarily ancestral alleles of two functional polymorphisms in the beta(2)-adrenergic receptor gene (ADRB2) were related to higher cognitive ability in the 70 year old participants of the Lothian Birth Cohort 1936 (LBC1936). One emerging important factor in cognitive aging is the integrity of white matter tracts in the brain. Here, we used diffusion tensor MRI-based tractography to assess the integrity of eight white matter tracts in a subsample of the LBC1936. Higher integrity of the splenium of the corpus callosum predicted better cognitive ability in old age, even after controlling for IQ at age 11. Also, the ancestral allele of one ADRB2 SNP was associated with both splenium integrity and better cognitive aging. While the effects of the SNP and splenium integrity on cognitive aging were largely independent, there was some evidence for a partial mediation effect of ADRB2 status via splenium integrity.

Disease symptomatology and response to treatment in people with idiopathic hypersomnia: initial data from the Hypersomnia Foundation registry.

OBJECTIVE/BACKGROUND: Knowledge of idiopathic hypersomnia symptomatology derives from clinical case series. Web-based registries provide complementary information by allowing larger sample sizes, with greater geographic and social diversity. PATIENTS/METHODS: Data were obtained from the Hypersomnia Foundation's online registry. Common clinical features of idiopathic hypersomnia and other central disorders of hypersomnolence were queried, for the last thirty days and when symptoms were most severe. Symptoms were compared between idiopathic hypersomnia participants with and without long sleep durations and between participants with idiopathic hypersomnia and those with either form of narcolepsy. Frequency of medication use and residual symptoms on medication were evaluated. RESULTS: Five-hundred sixty-three registry respondents were included, with idiopathic hypersomnia (n = 468), narcolepsy type 2 (n = 44), and narcolepsy type 1 (n = 51). "Brain fog," poor memory, and sleep drunkenness were all present in most idiopathic hypersomnia respondents, with brain fog and sleep drunkenness more commonly endorsed by those with long sleep durations. Eighty-two percent of participants with idiopathic hypersomnia were currently treated with medication, most commonly traditional psychostimulants such as amphetamine salts. Among treated patients, symptoms improved while on medication, but substantial residual hypersomnia symptoms remained. Participants with narcolepsy type 1 were more likely than those with idiopathic hypersomnia to endorse intentional and unintentional daytime naps and automatic behaviors. CONCLUSIONS: Symptoms of idiopathic hypersomnia extend well beyond excessive daytime sleepiness, and these symptoms frequently persist despite treatment. These findings highlight the importance of online registries in identifying gaps in the use and effectiveness of current treatments.

Bovine viral diarrhea virus core is an intrinsically disordered protein that binds RNA.

Pestiviruses, including bovine viral diarrhea virus (BVDV), are important animal pathogens and close relatives of hepatitis C virus. Pestivirus particles are composed of an RNA genome, a host-derived lipid envelope, and four virion-encoded structural proteins, core (C), E(rns), E1, and E2. Core is a small, highly basic polypeptide that is processed by three enzymatic cleavages before its incorporation into virions. Little is known about its biological properties or its role in virion assembly and structure. We have purified BVDV core protein and characterized it biochemically. We have determined that the processed form of core lacks significant secondary structure and is instead intrinsically disordered. Consistent with its highly basic sequence, we observed that core binds to RNA, although with low affinity and little discernible specificity. We found that BVDV core protein was able to functionally replace the nonspecific RNA binding and condensing region of an unrelated viral capsid protein. Together these results suggest that the in vitro properties of core may reflect its mechanism of action in RNA packaging and virion morphogenesis.