Discovery of novel inhibitors of histone deacetylase 6: Structure-based virtual screening, molecular dynamics simulation, enzyme inhibition and cell viability assays.

Histone deacetylase 6 (HDAC6) contributes to cancer metastasis in several cancers, including triple-negative breast cancer (TNBC)-the most lethal form that lacks effective therapy. Although several efforts have been invested to develop selective HDAC6 inhibitors, none have been approved by the FDA. Toward this goal, existing computational studies used smaller compound libraries and shorter MD simulations. Here, we conducted a structure-based virtual screening of ZINC "Druglike" library containing 17,900,742 compounds using a Glide virtual screening protocol comprising various filters with increasing accuracy. The top 20 hits were subjected to molecular dynamics simulation, MM-GBSA binding energy calculations, and further ADMET prediction. Furthermore, enzyme inhibition assay and cell viability assay were performed on six available compounds from the identified hits. C4 (ZINC000077541942) with a good profile of predicted drug properties was found to inhibit HDAC6 (IC50: 4.7 ± 11.6 µM) with comparative affinity to that of the known HDAC6 selective inhibitor Tubacin (TA) in our experiments. C4 also demonstrated cytotoxic effects against triple-negative breast cancer (TNBC) cell line MDA-MB-231 with EC50 of 40.6 ± 12.7 µM comparable to that of TA (2-20 µM). Therefore, this compound, with pharmacophore features comprising a non-hydroxamic acid zinc-binding group, heteroaromatic linker, and cap group, is proposed as a novel HDAC6 inhibitor.

Probing the Activation Mechanisms of Agonist DPI-287 to Delta-Opioid Receptor and Novel Agonists Using Ensemble-Based Virtual Screening with Molecular Dynamics Simulations.

Pain drugs targeting mu-opioid receptors face major addiction problems that have caused an epidemic. The delta-opioid receptor (DOR) has shown to not cause addictive effects when bound to an agonist. While the active conformation of the DOR in complex with agonist DPI-287 has been recently solved, there are still no FDA-approved agonists targeting it, providing the opportunity for structure-based virtual screening. In this study, the conformational plasticity of the DOR was probed using molecular dynamics (MD) simulations, identifying two representative conformations from clustering analysis. The two MD conformations as well as the crystal conformation of DOR were used to screen novel compounds from the ZINC database (17 million compounds), in which 69 drugs were picked as potential compounds based on their docking scores. Notably, 37 out of the 69 compounds were obtained from the simulated conformations. The binding stability of the 69 compounds was further investigated using MD simulations. Based on the MM-GBSA binding energy and the predicted drug properties, eight compounds were chosen as the most favorable, six of which were from the simulated conformations. Using a dynamic network model, the communication between the crystal agonist and the top eight molecules with the receptor was analyzed to confirm if these novel compounds share a similar activation mechanism to the crystal ligand. Encouragingly, docking of these eight compounds to the other two opioid receptors (kappa and mu) suggests their good selectivity toward DOR.

Perception of burden of oral and inhaled corticosteroid adverse effects on asthma-specific quality of life.

BACKGROUND: A multistakeholder core outcome set created for asthma trials showed that asthma-specific quality of life (QoL) was a critically meaningful outcome. However, the definition and measurement methods were undetermined. The adverse effects (AEs) of corticosteroids may be a vital clinical trial outcome. Nevertheless, the AE burden from the patient perspective has not yet been elucidated in an asthma population. OBJECTIVE: To characterize patient burden of AEs in oral (OCS) and inhaled corticosteroids (ICS) and how this relates to QoL within an asthma population. METHODS: We used a convergent parallel mixed-methods design with quantitative surveys of known ICS and OCS AEs that were distributed through the Allergy & Asthma Network database, social channels, and the Asthma UK newsletter. Participants rated the AEs that were (1) most burdensome and (2) most desired to be eliminated. Qualitative interviews and focus groups were performed to better understand patient views on barriers reported in the quantitative data, and to identify patient-important barriers that were not a part of the quantitative survey. RESULTS: The 3 most burdensome AEs for OCS were bone mineral density, infectious complications, and weight gain, whereas weight gain was the most desired to be eliminated. The 3 most burdensome AEs for ICS were pneumonia, hoarse voice, and oral thrush, with concordant results for the most desired to be eliminated. In the focus groups, OCS AEs were concordant with quantitative findings. Focus groups identified unmeasured psychosocial effects, such as embarrassment. CONCLUSION: The most burdensome AEs may not be those that would cause patients to stop therapy. Furthermore, qualitative focus groups suggest a psychosocial burden associated with ICS, which needs further investigation.

Investigating Social Media to Evaluate Emergency Medicine Physicians' Emotional Well-being During COVID-19.

Importance: Emergency medicine (EM) physicians experience tremendous emotional health strain, which has been exacerbated during COVID-19, and many have taken to social media to express themselves. Objective: To analyze social media content from academic EM physicians and resident physicians to investigate changes in content and language as indicators of their emotional well-being. Design, Setting, and Participants: This cross-sectional study used machine learning and natural language processing of Twitter posts from self-described academic EM physicians and resident physicians between March 2018 and March 2022. Participants included academic EM physicians and resident physicians with publicly accessible posts (at least 300 total words across the posts) from the US counties with the top 10 COVID-19 case burdens. Data analysis was performed from June to September 2022. Exposure: Being an EM physician or resident physician who posted on Twitter. Main Outcomes and Measures: Social media content themes during the prepandemic period, during the pandemic, and across the phases of the pandemic were analyzed. Psychological constructs evaluated included anxiety, anger, depression, and loneliness. Positive and negative language sentiment within posts was measured. Results: This study identified 471 physicians with a total of 198 867 posts (mean [SD], 11 403 [18 998] words across posts; median [IQR], 3445 [1100-11 591] words across posts). The top 5 prepandemic themes included free open-access medical education (Cohen d, 0.44; 95% CI, 0.38-0.50), residency education (Cohen d, 0.43; 95% CI, 0.37-0.49), gun violence (Cohen d, 0.37; 95% CI, 0.32-0.44), quality improvement in health care (Cohen d, 0.33; 95% CI, 0.27-0.39), and professional resident associations (Cohen d, 0.33; 95% CI, 0.27-0.39). During the pandemic, themes were significantly related to healthy behaviors during COVID-19 (Cohen d, 0.83; 95% CI, 0.77-0.90), pandemic response (Cohen d, 0.71; 95% CI, 0.65-0.77), vaccines and vaccination (Cohen d, 0.60; 95% CI, 0.53-0.66), unstable housing and homelessness (Cohen d, 0.40; 95% CI, 0.34-0.47), and emotional support for others (Cohen d, 0.40; 95% CI, 0.34-0.46). Across the phases of the pandemic, thematic content within social media posts changed significantly. Compared with the prepandemic period, there was significantly less positive, and concordantly more negative, language used during COVID-19. Estimates of loneliness, anxiety, anger, and depression also increased significantly during COVID-19. Conclusions and Relevance: In this cross-sectional study, key thematic shifts and increases in language related to anxiety, anger, depression, and loneliness were identified in the content posted on social media by academic EM physicians and resident physicians during the pandemic. Social media may provide a real-time and evolving landscape to evaluate thematic content and linguistics related to emotions and sentiment for health care workers.

Extrascleral extension of choroidal melanoma after iodine-125 brachytherapy treatment: a case series.

BACKGROUND/OBJECTIVES: The purpose of this study is to report cases of choroidal melanoma that developed extrascleral tumour recurrence after treatment with iodine-125 brachytherapy. SUBJECTS/METHODS: In this single-institution retrospective observational case series, all instances of biopsy-confirmed orbital melanoma after known intraocular melanoma were reviewed. Tumour characteristics, clinical course, time to recurrence, cytogenetics of initial tumour and recurrence, and presence of intraocular recurrence were documented. RESULTS: Five cases of orbital melanoma following treatment with plaque radiotherapy are described. Tumour staging was Ia (1), IIa (2), and IIb (2). The primary lesion in four of the five appeared to have undergone complete regression for an average of 2 years, with the orbital melanoma developing after this interval. Recurrence of the intraocular tumour was seen in conjunction with an extrascleral component in two cases. Four cases ultimately underwent enucleation or exenteration; three had evidence of direct extension of tumour through the sclera. Four cases in this series had molecular characteristics associated with high metastatic risk (three patients with monosomy 3, one with BAP1 mutation). CONCLUSIONS: High-risk tumour biology may predispose to late appearance of extrascleral melanoma despite optimal treatment and adequate control of the intraocular tumour. Extended follow-up with detailed orbital examination and imaging is recommended for this population.

Effect of external eyelid weighting on eyelid and eyebrow position in normal and ptosis patients.

PURPOSE: This study aims to characterize the physiologic response of both eyelid and eyebrow position to increasing downward forces simulated by external weights. METHODS: In this prospective observational study, both normal individuals and patients affected by ptosis were tested. External eyelid weights were placed on one upper eyelid with incrementally increasing weight from 0.2 to 2.4 g. The eyelid carrying the weight was randomly selected for normal subjects and patients with bilateral ptosis, whereas for unilateral ptosis, the ptotic eyelid was utilized. Photographs were obtained at baseline and with increasing weight until MRD1 reached 0 on the weighted side or, until 2.4 g was reached. Eyelid and brow position on the weighted and unweighted sides were digitally measured in millimeter. Primary outcome measures were change in the margin to reflex distance (MRD1) and pupil to brow distance (PTB) with weight on the weighted and unweighted sides for normal and ptosis subjects. RESULTS: The weighted eyelid MRD1 decreased linearly with increasing weight. This was true for normal and ptosis subjects. The unweighted eyelid MRD1 increased linearly with increasing weight. This was also the case for both normal and ptosis subjects. With increasing weight, PTB increased linearly on the weighted side. No significant intergroup differences were noted. CONCLUSIONS: In normal and ptosis subjects, when external weight on the eyelid is incrementally increased, the weighted eyelid MRD1 decreases, the unweighted eyelid MRD1 increases, and both brows elevate in a linear fashion.

Novel inhibitors to ADP ribose phosphatase of SARS-CoV-2 identified by structure-based high throughput virtual screening and molecular dynamics simulations.

The outbreak of a new coronavirus (SARS-CoV-2) was first identified in Wuhan, People's Republic of China, in 2019, which has led to a severe, life-threatening form of pneumonia (COVID-19). Research scientists all around the world have been trying to find small molecule drugs to treat COVID-19. In the present study, a conserved macrodomain, ADP Ribose phosphatase (ADRP), of a critical non-structural protein (Nsp3) in all coronaviruses was probed using large-scale Molecular Dynamics (MD) simulations to identify novel inhibitors. In our virtual screening workflow, the recently-solved X-ray complex structure, 6W6Y, with a substrate-mimics was used to screen 17 million ZINC15 compounds using drug property filters and Glide docking scores. The top twenty output compounds each underwent 200 ns MD simulations (i.e. 20 × 200 ns) to validate their individual stability as potential inhibitors. Eight out of the twenty compounds showed stable binding modes in the MD simulations, as well as favorable drug properties from our predctions. Therefore, our computational data suggest that the resulting top eight out of twenty compounds could potentially be novel inhibitors to ADRP of SARS-CoV-2.

A multistakeholder Delphi consensus core outcome set for clinical trials in moderate-to-severe asthma (coreASTHMA).

BACKGROUND: Treatments for long-term control of asthma have improved and include a promising but expensive class of biologic therapies. However, the clinical trials evaluating these and other novel treatments have used a variety of different outcomes to evaluate efficacy. The evolution of asthma care calls for a re-examination of outcomes that are most important to patients and other stakeholders. OBJECTIVE: To develop a core set of outcomes to be measured in phase 3 and phase 4 clinical drug trials in patients with moderate-to-severe asthma. METHODS: We used a robust and in-depth multistakeholder consensus process bringing together patients, clinicians, regulators, payers, health technology assessors, researchers, and product developers to reach consensus on outcomes. We used a modified Delphi method to reach consensus, an approach adapted from the Core Outcome Measures in Effectiveness Trials Initiative aligned with contemporary methodological standards for core outcome set development. RESULTS: The following outcomes were included in the final core set: severe asthma exacerbation, change in asthma control, asthma-specific or severe asthma-specific quality of life, asthma-specific hospital stay (ie, >24-hour stays at any level of care) or admission, and asthma-specific emergency department visit. CONCLUSION: These 5 outcomes represent a minimum set of core outcomes for use in phase 3 and phase 4 clinical drug trials in moderate-to-severe asthma. Consistent collection of these outcomes as minimum, independent of whether additional heterogeneous primary or secondary outcomes are included, will allow for meaningful comparisons of the effect of asthma therapies across clinical trials.

Effect of clinical pharmacist interventions on cost in an integrated health system specialty pharmacy.

BACKGROUND: Patients who are prescribed specialty medications require close monitoring, including assessment of laboratory parameters, toxicities, and adherence. Specialty pharmacies integrated within a health system are able to access records, assess therapy, and efficiently communicate with prescribers. OBJECTIVE: To analyze interventions made by clinical pharmacists within the Cleveland Clinic Specialty Pharmacy (CCSP) regarding cost avoidance for the health care system and improvements in patient safety. METHODS: This was a retrospective, observational study that analyzed pharmacist interventions regarding specialty hematology/oncology medications. Interventions were measured with pharmacist documentation within the electronic health record (EHR). The primary endpoint was the cost-avoidance effect of clinical pharmacist interventions resulting from pharmacist access to the EHR. Secondary endpoints included pharmacist interventions that led to additional ancillary or supportive care, time taken to perform interventions, total interventions according to new or refill status, and total interventions performed according to insurance subtype. RESULTS: 547 interventions were identified during the study period, with a total cost avoidance of $1,508,131. The intervention with the highest overall cost savings was discontinuation of therapy ($290,091). The highest cost savings, based on intervention type, was lack of follow-up ($30,892). The medication with the highest overall cost savings was abiraterone ($273,160). Gilteritinib was associated with the highest cost saving per intervention ($28,350). The indication with the highest overall cost savings was prostate cancer ($402,601), while cutaneous T-cell lymphoma had the highest cost savings per intervention ($25,424). CONCLUSIONS: CCSP pharmacist interventions led to significant overall cost savings to the health care system. Although not measured in this study, it is reasonable to expect that decreased medication use may also translate into less financial burden for patients, as well as for pharmacy benefit managers. Access to the EHR and integration within the health care system may have facilitated the cost savings. DISCLOSURES: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to disclose.

The asthma evidence base: a call for core outcomes in interventional trials.

OBJECTIVES: Biologic therapies are emerging as an option to treat a subset of patients with severe asthma, however no direct comparison between these agents has been conducted. Furthermore, heterogeneity of outcomes in clinical trials makes it difficult to compare these agents and traditional therapies. The extent to which this heterogeneity exists has major implications for evidence-based decisions and is yet to be fully reported. We conducted a literature search to examine outcomes currently being used in clinical trials for asthma. DATA SOURCES: The Cochrane Library and Clinicaltrials.gov were searched for clinical trials of asthma interventions. STUDY SELECTIONS: We limited our search to phase 2 through 4 clinical trials in adults, as early-phase trials tend to have pharmacodynamic and pharmacokinetic endpoints as primary outcomes. Interventions for acute exacerbations were excluded. RESULTS: We identified 117 studies and subsequently identified 111 outcomes. The most prevalent outcomes were asthma control and symptom severity, FEV1, and change in ACQ scale. Twenty patient-reported outcomes instruments were identified and de-facto standard asthma outcomes and PROs were under-reported in examined literature. Existing quality of life tools did not capture the day-to-day experience or the unique treatment burden from oral corticosteroids for patient with severe asthma. Compounding the absence of trials directly comparing therapies, the significant variation we identified in outcome definitions and measurement create hurdles to effectively compare traditional and biologic therapies. CONCLUSION: With the growing number of clinical trials evaluating advanced therapies such as biologics, a wide range of primary and secondary outcomes are evaluated. A core outcome set created by relevant stakeholders is needed to collectively evaluate pooled outcomes in order to allow more meaningful comparisons of asthma therapies and to incorporate the patient experience.

Quantification of Retinal Nonperfusion and Neovascularization With Ultrawidefield Fluorescein Angiography in Patients With Diabetes and Associated Characteristics of Advanced Disease.

Importance: Quantification of nonperfusion (NP) and neovascularization (NV) in diabetic retinopathy (DR) may identify better biomarkers of disease progression. Objective: To identify demographic risk factors and markers of advanced DR that are associated with increased areas of NP and NV in eyes with disease ranging from no DR but diagnosed as having diabetes to proliferative DR (PDR) and to calculate a threshold total area of NP that may be associated with an increased risk of PDR. Design, Setting, and Participants: This retrospective case series was performed on ultrawidefield fluorescein angiography (UWF FA) images from January 2009 to May 2018 at the University of Michigan Kellogg Eye Center. A total of 363 participants (651 eyes) diagnosed as having type 1 or 2 diabetes receiving UWF FA were included. Exclusion criteria included previous panretinal photocoagulation (PRP) and poor-quality images (eg, vitreous hemorrhage and significant cataract). Main Outcomes and Measures: The surface areas in millimeters squared of the foveal avascular zone; total NP; NP at posterior pole, midperiphery, and far periphery; total NV; NV at posterior pole, midperiphery, and far periphery were measured. Results: Of 363 patients, most were male (205 patients [56.5%]) and white (247 [68%]) or black (77 [21.2%]). The mean (SD) age was 59.4 (13.7) years. Seventy-six eyes with no DR, 92 with mild NPDR, 144 with moderate NPDR, 101 with severe NPDR, 220 with PDR, and 18 with DR of unknown severity were included. Male sex had a positive association with total NP (difference, 15.72; 95% CI, 4.83-26.61; P = .005); black race/ethnicity with total NV (difference, 2.32; 95% CI, 0.09-4.55; P = .04); and vitreous hemorrhage with total NP (difference, 30.00; 95% CI, 5.26-54.75; P = .02). A threshold total NP area of 77.48 mm2 (95% CI, 54.24-92.66 mm2) was identified, at greater than which patients may have an increased risk of developing PDR (sensitivity of 59.5% and specificity of 73.6%). Conclusions and Relevance: Our results indicate NP and NV can be quantified on UWF FA. These biomarkers interpreted with demographic risk factors may help predict disease progression. Conclusions are limited by ascertainment and information biases because the results are from retrospective data.

Addressing heterogenous outcomes in uterine fibroid research: a call to action.

Uterine fibroid tumors are the most common benign pelvic tumors in women, with complications that include heavy menstrual bleeding, pelvic pain, reproductive complications, and bulk-related symptoms. Although the majority of uterine fibroid tumors are asymptomatic, those women who experience symptoms can experience substantial burdens on quality of life and daily functioning. Comparative effectiveness reviews of available medical, surgical, and radiologic treatments have found that a lack of high-quality data to inform treatment decisions is, in part, due to the use of heterogeneous outcomes and instruments in clinical studies. With multiple new interventions emerging, this call-to-action encourages the development and use of a core outcome set that will capture the most relevant, patient-important outcomes in late-phase and after-marketing therapeutic trials for uterine fibroid tumors. The core outcome set should be developed by a diverse, multistakeholder group comprised of key healthcare decision-makers. Development and uptake of a core outcome set ensures that a consistent, collaboratively vetted set of outcomes will be accessible across different studies and promotes transparency for innovators who seek to anticipate the evidence needs of patients, providers, payers, regulators, and other stakeholders.

Differences in Career Satisfaction, Work-life Balance, and Stress by Gender in a National Survey of Pharmacy Faculty.

INTRODUCTION: The percentage of women pharmacy students and pharmacy faculty has greatly increased over the last 40 years. However, it is not known whether gender differences exist in terms of career satisfaction, work-life balance, and stress in the pharmacy academia workplace. METHODS: Results from a national web-based survey administered to American Association of Colleges of Pharmacy (AACP) members were utilized. Bivariate analyses were conducted to compare differences among faculty according to gender (men vs women). A series of multivariate models controlling for demographic and other faculty and school-level factors were created to explore the impact of gender on satisfaction with current position, satisfaction with work-life balance, and perceived stress. RESULTS: Among the 802 survey respondents, 457 (57.0%) women were more likely to be younger, hold a lower academic rank, and be in a pharmacy practice department, relative to 345 (43.0%) men. In adjusted results, men pharmacy faculty were more likely to report being extremely satisfied with their current job, more likely to report being extremely satisfied with their work-life balance, and score lower on a standardized stress measure relative to women. CONCLUSION: While primarily descriptive, the results suggest women pharmacy faculty in the United States are less satisfied with their current academic position, less satisfied with their current work-life balance, and have higher stress levels compared to men even after controlling for age, academic rank, and department (along with other factors). Further research is needed to explore and address causes of the observed gender-related differences among pharmacy faculty.

Alopecia Areata is Associated with Increased Expression of Heart Disease Biomarker Cardiac Troponin I.

The development of androgenetic alopecia is associated with a risk of developing cardiovascular diseases, but the association of alopecia areata with cardiovascular diseases in humans is largely unexplored. We measured the plasma level of two common cardiovascular disease markers, cardiac troponin I and C-reactive protein, in alopecia areata and androgenetic alopecia affected subjects. Also, we investigated the possible presence of pro-apoptotic factors in the plasma of hair loss subjects. The mean plasma cardiac troponin I level was highest in alopecia areata subjects, moderately higher in androgenetic alopecia subjects, and lowest in subjects without hair loss (p <0.05). Alopecia areata subjects not receiving treatments had highest levels of cTnI (p <0.05). Alopecia areata plasma samples with high cardiac troponin I levels also induced significantly higher rates of cardiomyocyte apoptosis in cell culture assays. The results suggest the potential for increased heart remodelling. Close monitoring of cardiovascular health in alopecia areata subjects, as well as subsets of androgenetic alopecia patients, may be appropriate.

Impact of the Act FAST stroke campaign delivered by student pharmacists on the primary prevention of stroke.

OBJECTIVES: To evaluate the impact of an Act FAST educational intervention performed by student pharmacists on knowledge of stroke recognition and management. DESIGN: Stroke preparedness and knowledge of primary prevention were assessed with the use of pre- and post-intervention surveys targeting community members at health fairs. The intervention was an Act FAST educational session with blood pressure and blood glucose screenings provided by student pharmacists. Act FAST is a quick tool to help recognize and respond to a stroke. The acronym FAST stands for Face, Arms, Speech, and Time. SETTING: Community health fairs in Vallejo, CA. PARTICIPANTS: Community members 18 years of age and older. INTERVENTION: Act FAST educational session delivered by student pharmacists. MAIN OUTCOME MEASURES: Knowledge of signs, symptoms, management, and risk factors of strokes as defined by the American Heart Association. RESULTS: Following the Act FAST educational intervention, total knowledge of signs, symptoms, and management of stroke significantly increased from moderate to high (n = 112; 95% confidence interval [CI] 1.419-2.188; P <0.0001). Total knowledge of risk factors of stroke also significantly increased following the educational intervention (n = 88; 95% CI 0.6496-1.746; P <0.0001). CONCLUSION: The Act FAST educational intervention delivered by student pharmacists increased knowledge of signs, symptoms, immediate management, and modifiable risk factors of stroke. This suggests that student pharmacists may have a positive impact on community members' preparedness and knowledge of primary prevention of stroke. The Act FAST campaign may be a useful tool for all training health care professionals.

Visual attention is required for multiple object tracking.

In the multiple object tracking task, participants attempt to keep track of a moving set of target objects embedded in an identical set of moving distractors. Depending on several display parameters, observers are usually only able to accurately track 3 to 4 objects. Various proposals attribute this limit to a fixed number of discrete indexes (Pylyshyn, 1989), limits in visual attention (Cavanagh & Alvarez, 2005), or "architectural limits" in visual cortical areas (Franconeri, 2013). The present set of experiments examined the specific role of visual attention in tracking using a dual-task methodology in which participants tracked objects while identifying letter probes appearing on the tracked objects and distractors. As predicted by the visual attention model, probe identification was faster and/or more accurate when probes appeared on tracked objects. This was the case even when probes were more than twice as likely to appear on distractors suggesting that some minimum amount of attention is required to maintain accurate tracking performance. When the need to protect tracking accuracy was relaxed, participants were able to allocate more attention to distractors when probes were likely to appear there but only at the expense of large reductions in tracking accuracy. A final experiment showed that people attend to tracked objects even when letters appearing on them are task-irrelevant, suggesting that allocation of attention to tracked objects is an obligatory process. These results support the claim that visual attention is required for tracking objects. (PsycINFO Database Record

Indicators for chronic disease surveillance - United States, 2013.

Chronic diseases are an important public health problem, which can result in morbidity, mortality, disability, and decreased quality of life. Chronic diseases represented seven of the top 10 causes of death in the United States in 2010 (Murphy SL, Xu J, Kochanek KD. Deaths: final data for 2010. Natl Vital Stat Rep 2013;6. Available at http://www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_04.pdf Adobe PDF file). Chronic diseases and risk factors vary by geographic area such as state and county, where essential public health interventions are implemented. The chronic disease indicators (CDIs) were established in the late 1990s through collaboration among CDC, the Council of State and Territorial Epidemiologists, and the Association of State and Territorial Chronic Disease Program Directors (now the National Association of Chronic Disease Directors) to enable public health professionals and policymakers to retrieve data for chronic diseases and risk factors that have a substantial impact on public health. This report describes the latest revisions to the CDIs, which were developed on the basis of a comprehensive review during 2011-2013. The number of indicators is increasing from 97 to 124, with major additions in systems and environmental indicators and additional emphasis on high-impact diseases and conditions as well as emerging topics.

Alcohol-attributable deaths and years of potential life lost--11 States, 2006-2010.

Excessive alcohol consumption, the fourth leading preventable cause of death in the United States, resulted in approximately 88,000 deaths and 2.5 million years of potential life lost (YPLL) annually during 2006-2010 and cost an estimated $223.5 billion in 2006. To estimate state-specific average annual rates of alcohol-attributable deaths (AAD) and YPLL caused by excessive alcohol use, 11 states analyzed 2006-2010 data (the most recent data available) using the CDC Alcohol-Related Disease Impact (ARDI) application. The age-adjusted median AAD rate was 28.5 per 100,000 population (range = 50.9 per 100,000 in New Mexico to 22.4 per 100,000 in Utah). The median YPLL rate was 823 per 100,000 (range = 1,534 YPLL per 100,000 for New Mexico to 634 per 100,000 in Utah). The majority of AAD (median = 70%) and YPLL (median = 82%) were among working-age (20-64 years) adults. Routine monitoring of alcohol-attributable health outcomes, including deaths and YPLL, in states could support the planning and implementation of evidence-based prevention strategies recommended by the Community Preventive Services Task Force to reduce excessive drinking and related harms. Such strategies include increasing the price of alcohol, limiting alcohol outlet density, and holding alcohol retailers liable for harms related to the sale of alcoholic beverages to minors and intoxicated patrons (dram shop liability).

Infants' Response to Pictures of Impossible Objects.

Previous work has shown that 4-month-olds can discriminate between two-dimensional (2D) depictions of structurally possible and impossible objects [S. M. Shuwairi (2009), Journal of Experimental Child Psychology, 104, 115; S. M. Shuwairi, M. K. Albert, & S. P. Johnson (2007), Psychological Science, 18, 303]. Here, we asked whether evidence of discrimination of possible and impossible pictures would also be revealed in infants' patterns of reaching and manual exploration. Nine-month-old infants were presented with realistic photograph displays of structurally possible and impossible cubes along with a series of perceptual controls, and engaged in more frequent manual exploration of pictures of impossible objects. In addition, the impossible cube display elicited significantly more social referencing and vocalizations than the possible cube and perceptual control displays. The increased manual gestures associated with the incoherent figure suggest that perceptual and manual action mechanisms are interrelated in early development. The infant's visual system extracts structural information contained in 2D images in analyzing the projected 3D configuration, and this information serves to control both the oculomotor and manual action systems.