Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma.

BACKGROUND: Traumatic acute subdural hematomas frequently warrant surgical evacuation by means of a craniotomy (bone flap replaced) or decompressive craniectomy (bone flap not replaced). Craniectomy may prevent intracranial hypertension, but whether it is associated with better outcomes is unclear. METHODS: We conducted a trial in which patients undergoing surgery for traumatic acute subdural hematoma were randomly assigned to undergo craniotomy or decompressive craniectomy. An inclusion criterion was a bone flap with an anteroposterior diameter of 11 cm or more. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOSE) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 12 months. Secondary outcomes included the GOSE rating at 6 months and quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L). RESULTS: A total of 228 patients were assigned to the craniotomy group and 222 to the decompressive craniectomy group. The median diameter of the bone flap was 13 cm (interquartile range, 12 to 14) in both groups. The common odds ratio for the differences across GOSE ratings at 12 months was 0.85 (95% confidence interval, 0.60 to 1.18; P = 0.32). Results were similar at 6 months. At 12 months, death had occurred in 30.2% of the patients in the craniotomy group and in 32.2% of those in the craniectomy group; a vegetative state occurred in 2.3% and 2.8%, respectively, and a lower or upper good recovery occurred in 25.6% and 19.9%. EQ-5D-5L scores were similar in the two groups at 12 months. Additional cranial surgery within 2 weeks after randomization was performed in 14.6% of the craniotomy group and in 6.9% of the craniectomy group. Wound complications occurred in 3.9% of the craniotomy group and in 12.2% of the craniectomy group. CONCLUSIONS: Among patients with traumatic acute subdural hematoma who underwent craniotomy or decompressive craniectomy, disability and quality-of-life outcomes were similar with the two approaches. Additional surgery was performed in a higher proportion of the craniotomy group, but more wound complications occurred in the craniectomy group. (Funded by the National Institute for Health and Care Research; RESCUE-ASDH ISRCTN Registry number, ISRCTN87370545.).

Myeloid Cell Derived IL1ß Contributes to Pulmonary Hypertension in HFpEF.

BACKGROUND: Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are poorly understood. We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF. METHODS: Eight-week-old male and female C57BL/6J mice received either Nγ-nitro-L-arginine methyl ester and high-fat diet or control water and diet for 2, 5, and 12 weeks. The db/db mice were studied as a second model of HFpEF. Early pathways regulating PH were identified by bulk and single-cell RNA sequencing. Findings were confirmed by immunostain in lungs of mice or lung slides from clinically performed autopsies of patients with PH-HFpEF. ELISA was used to verify IL-1ß (interleukin-1 beta) in mouse lung, mouse plasma, and also human plasma from patients with PH-HFpEF obtained at the time of right heart catheterization. Clodronate liposomes and an anti-IL-1ß antibody were utilized to deplete macrophages and IL-1ß, respectively, to assess their impact on pulmonary vascular remodeling in HFpEF in mouse models. RESULTS: Nγ-nitro-L-arginine methyl ester/high-fat diet-treated mice developed PH, small vessel muscularization, and right heart dysfunction. Inflammation-related gene ontologies were overrepresented in bulk RNA sequencing analysis of whole lungs, with an increase in CD68+ cells in both murine and human PH-HFpEF lungs. Cytokine profiling showed an increase in IL-1ß in mouse and human plasma. Finally, clodronate liposome treatment in mice prevented PH in Nγ-nitro-L-arginine methyl ester/high-fat diet-treated mice, and IL-1ß depletion also attenuated PH in Nγ-nitro-L-arginine methyl ester/high-fat diet-treated mice. CONCLUSIONS: We report a novel model for the study of PH and right heart remodeling in HFpEF, and we identify myeloid cell-derived IL-1ß as an important contributor to PH in HFpEF.

Associations of neighborhood sociodemographic environment with mortality and circulating metabolites among low-income black and white adults living in the southeastern United States.

BACKGROUND: Residing in a disadvantaged neighborhood has been linked to increased mortality. However, the impact of residential segregation and social vulnerability on cause-specific mortality is understudied. Additionally, the circulating metabolic correlates of neighborhood sociodemographic environment remain unexplored. Therefore, we examined multiple neighborhood sociodemographic metrics, i.e., neighborhood deprivation index (NDI), residential segregation index (RSI), and social vulnerability index (SVI), with all-cause and cardiovascular disease (CVD) and cancer-specific mortality and circulating metabolites in the Southern Community Cohort Study (SCCS). METHODS: The SCCS is a prospective cohort of primarily low-income adults aged 40-79, enrolled from the southeastern United States during 2002-2009. This analysis included self-reported Black/African American or non-Hispanic White participants and excluded those who died or were lost to follow-up ≤ 1 year. Untargeted metabolite profiling was performed using baseline plasma samples in a subset of SCCS participants. RESULTS: Among 79,631 participants, 23,356 deaths (7214 from CVD and 5394 from cancer) were documented over a median 15-year follow-up. Higher NDI, RSI, and SVI were associated with increased all-cause, CVD, and cancer mortality, independent of standard clinical and sociodemographic risk factors and consistent between racial groups (standardized HRs among all participants were 1.07 to 1.20 in age/sex/race-adjusted model and 1.04 to 1.08 after comprehensive adjustment; all P < 0.05/3 except for cancer mortality after comprehensive adjustment). The standard risk factors explained < 40% of the variations in NDI/RSI/SVI and mediated < 70% of their associations with mortality. Among 1110 circulating metabolites measured in 1688 participants, 134 and 27 metabolites were associated with NDI and RSI (all FDR < 0.05) and mediated 61.7% and 21.2% of the NDI/RSI-mortality association, respectively. Adding those metabolites to standard risk factors increased the mediation proportion from 38.4 to 87.9% and 25.8 to 42.6% for the NDI/RSI-mortality association, respectively. CONCLUSIONS: Among low-income Black/African American adults and non-Hispanic White adults living in the southeastern United States, a disadvantaged neighborhood sociodemographic environment was associated with increased all-cause and CVD and cancer-specific mortality beyond standard risk factors. Circulating metabolites may unveil biological pathways underlying the health effect of neighborhood sociodemographic environment. More public health efforts should be devoted to reducing neighborhood environment-related health disparities, especially for low-income individuals.

The clinical relevance of the new criteria for cirrhotic cardiomyopathy and future directions.

Cardiac dysfunction in patients with liver disease has been recognized since the 1950s. Initially attributed to shared risk factors, it is now evident that cardiac dysfunction in patients with cirrhosis can occur in the absence of known cardiac, i.e., coronary artery and valvular heart disease, and across all etiologies for cirrhosis. In 1996 this myocardial dysfunction was termed cirrhotic cardiomyopathy (CCM). The pathophysiologic mechanisms underlying CCM include impaired beta-adrenergic membrane function and circulating proinflammatory and cardiotoxic substances. In 2005, the first diagnostic criteria for CCM were introduced enabling greater sensitivity and accuracy of diagnosis. Since 2005, advancements in echocardiographic methods and better understanding of the pathophysiology of cardiac dysfunction in patients with cirrhosis necessitated revision of CCM criteria. Changes in CCM criteria included removal of blunted contractile or heart rate response on stress testing and addition of global longitudinal systolic strain. Refinement of criteria for diastolic dysfunction were also incorporated into the new diagnostic approach. Since 2020, the prevalence of the disorder and clinical considerations for pre-transplant, peritransplant, and post-transplant patients with cirrhosis have been further evaluated and CCM was found to adversely impact clinical outcomes during all three phases of care. Future research considerations should address the timing of universal echocardiographic screening for patients with cirrhosis, utility of biomarkers in aiding CCM diagnosis, impact of CCM on right heart function, and role of anti-remodeling agents post-liver transplant (post-LT).

Racial differences in low natriuretic peptide levels: Implications for heart failure clinical trials.

BACKGROUND: Some patients with heart failure (HF) have low natriuretic peptide (NP) levels. It is unclear whether specific populations are disproportionately excluded from participation in randomized clinical trials (RCT) with inclusion requirements for elevated NPs. We investigated factors associated with unexpectedly low NP levels in a cohort of patients hospitalized with HF, and the implications on racial diversity in a prototype HF RCT. METHODS: We created a retrospective cohort of 31,704 patients (age 72 ± 16 years, 49% female, 52% Black) hospitalized with HF from 2010 to 2020 with B-type natriuretic peptide (BNP) measurements. Factors associated with unexpectedly low BNP levels (<50 pg/mL) were identified using multivariable logistic regression models. We simulated patient eligibility for a prototype HF trial using specific inclusion and exclusion criteria, and varying BNP cut-offs. RESULTS: Unexpectedly low BNP levels were observed in 8.9% of the cohort. Factors associated with unexpectedly low BNP levels included HFpEF (aOR 3.76, 95% CI: 3.36, 4.20), obesity (aOR 1.96, 95% CI: 1.73, 2.21), self-identification as Black (aOR 1.53, 95% CI: 1.36, 1.71), and male gender (aOR 1.45, 95% CI: 1.31, 1.60). Applying limited clinical inclusion and exclusion criteria from PARAGLIDE-HF disproportionately excluded Black patients, with impairment in renal function having the greatest impact. Adding thresholds for BNP of ≥35, ≥50, ≥67, ≥100, and ≥150 pg/mL demonstrated the risk of exclusion was higher for Black compared to non-Black patients (RR = 2.03 [95% CI: 1.73, 2.39], 1.90 [95% CI: 1.68, 2.15], 1.63 [95% CI: 1.48, 1.81], 1.38 [95% CI: 1.28, 1.50], and 1.23 [95% CI: 1.15, 1.31], respectively). CONCLUSIONS: Nearly 10% of patients hospitalized with HF have unexpectedly low BNP levels. Simulating inclusion into a prototype HFpEF RCT demonstrated that requiring increasingly elevated NP levels disproportionately excludes Black patients.

Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial.

OBJECTIVE: To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). BACKGROUND: Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit. METHODS: This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16-64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study. RESULTS: Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (- 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes. CONCLUSION: Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.

Effect of Dietary Sodium on Blood Pressure: A Crossover Trial.

Importance: Dietary sodium recommendations are debated partly due to variable blood pressure (BP) response to sodium intake. Furthermore, the BP effect of dietary sodium among individuals taking antihypertensive medications is understudied. Objectives: To examine the distribution of within-individual BP response to dietary sodium, the difference in BP between individuals allocated to consume a high- or low-sodium diet first, and whether these varied according to baseline BP and antihypertensive medication use. Design, Setting, and Participants: Prospectively allocated diet order with crossover in community-based participants enrolled between April 2021 and February 2023 in 2 US cities. A total of 213 individuals aged 50 to 75 years, including those with normotension (25%), controlled hypertension (20%), uncontrolled hypertension (31%), and untreated hypertension (25%), attended a baseline visit while consuming their usual diet, then completed 1-week high- and low-sodium diets. Intervention: High-sodium (approximately 2200 mg sodium added daily to usual diet) and low-sodium (approximately 500 mg daily total) diets. Main Outcomes and Measures: Average 24-hour ambulatory systolic and diastolic BP, mean arterial pressure, and pulse pressure. Results: Among the 213 participants who completed both high- and low-sodium diet visits, the median age was 61 years, 65% were female and 64% were Black. While consuming usual, high-sodium, and low-sodium diets, participants' median systolic BP measures were 125, 126, and 119 mm Hg, respectively. The median within-individual change in mean arterial pressure between high- and low-sodium diets was 4 mm Hg (IQR, 0-8 mm Hg; P < .001), which did not significantly differ by hypertension status. Compared with the high-sodium diet, the low-sodium diet induced a decline in mean arterial pressure in 73.4% of individuals. The commonly used threshold of a 5 mm Hg or greater decline in mean arterial pressure between a high-sodium and a low-sodium diet classified 46% of individuals as "salt sensitive." At the end of the first dietary intervention week, the mean systolic BP difference between individuals allocated to a high-sodium vs a low-sodium diet was 8 mm Hg (95% CI, 4-11 mm Hg; P < .001), which was mostly similar across subgroups of age, sex, race, hypertension, baseline BP, diabetes, and body mass index. Adverse events were mild, reported by 9.9% and 8.0% of individuals while consuming the high- and low-sodium diets, respectively. Conclusions and Relevance: Dietary sodium reduction significantly lowered BP in the majority of middle-aged to elderly adults. The decline in BP from a high- to low-sodium diet was independent of hypertension status and antihypertensive medication use, was generally consistent across subgroups, and did not result in excess adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT04258332.

Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease. RESULTS: Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Cross-species analysis between the maize smut fungi Ustilago maydis and Sporisorium reilianum highlights the role of transcriptional change of effector orthologs for virulence and disease.

The constitution and regulation of effector repertoires shape host-microbe interactions. Ustilago maydis and Sporisorium reilianum are two closely related smut fungi, which both infect maize but cause distinct disease symptoms. Understanding how effector orthologs are regulated in these two pathogens can therefore provide insights into the evolution of different infection strategies. We tracked the infection progress of U. maydis and S. reilianum in maize leaves and used two distinct infection stages for cross-species RNA-sequencing analyses. We identified 207 of 335 one-to-one effector orthologs as differentially regulated during host colonization, which might reflect the distinct disease development strategies. Using CRISPR-Cas9-mediated gene conversion, we identified two differentially expressed effector orthologs with conserved function between two pathogens. Thus, differential expression of functionally conserved genes might contribute to species-specific adaptation and symptom development. Interestingly, another differentially expressed orthogroup (UMAG_05318/Sr10075) showed divergent protein function, providing a possible case for neofunctionalization. Collectively, we demonstrated that the diversification of effector genes in related pathogens can be caused both by alteration on the transcriptional level and through functional diversification of the encoded effector proteins.

Active B-Type Natriuretic Peptide Measured by Mass Spectrometry and Response to Sacubitril/Valsartan.

BACKGROUND: B-type natriuretic peptide (BNP) immunoassays (BNPia) do not differentiate active and inactive forms. Inactive NT-proBNP is used to track heart failure (HF) during treatment with sacubitril/valsartan, which inhibits BNP degradation. Mass spectrometry (MS) may better assess effects of HF treatment on biologically active BNP1-32. METHODS AND RESULTS: We developed a MS assay with immediate protease inhibition to quantify BNP1-32 over a linear range, using labeled recombinant BNP standard. In 4 healthy volunteers, BNP1-32 by MS (BNPMS) increased from below the 5 pg/mL detection limit to 228 pg/mL after nesiritide. In patients with HF, BNPMS was measured in parallel with BNP and NT-proBNP immunoassays before and during sacubitril/valsartan treatment. BNPMS was 4.4-fold lower than BNPia in patients with HF. Among patients not taking sacubitril/valsartan and without end-stage renal disease, BNPMS correlated with BNPia (rs = 0.77, P < .001) and NT-proBNP (rs = 0.74, P < .001). After a median of 8 weeks on sacubitril/valsartan, active BNPMS levels decreased by 50% (interquartile range -98.3% to 41.7%, n = 22, P = .048) and correlated with NT-proBNP (rs = 0.64, P < .001), but not with BNPia (rs = 0.46, P = .057). CONCLUSIONS: Active BNP measured by MS accounts for only a small amount of BNP measured by immunoassays. Although decreased BNP production was anticipated to be masked by inhibition of degradation, levels of active BNP decreased during chronic sacubitril/valsartan treatment.

Distribution and Correlates of Incident Heart Failure Risk in South Asian Americans: The MASALA Study.

BACKGROUND: South Asian Americans experience disproportionately high burden of cardiovascular diseases. Estimating predicted heart failure (HF) risk distribution may facilitate targeted prevention. We estimated the distribution of 10-year predicted risk of incident HF in South Asian Americans and evaluated the associations with social determinants of health and clinical risk factors. METHODS AND RESULTS: In the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study, we calculated 10-year predicted HF risk using the Pooled Cohort Equations to Prevent Heart Failure multivariable model. Distributions of low (<1%), intermediate (1%-5%), and high (≥5%) HF risk, identified overall and by demographic and clinical characteristics, were compared. We evaluated age- and sex-adjusted associations of demographic characteristics and coronary artery calcium with predicted HF risk category using ordinal logistic regression. In 1159 participants (48% women), with a mean age of 57 ± 9 years, 40% had a low, 37% had an intermediate, and 24% had a high HF risk. Significant differences in HF risk distribution existed across demographic (income, education, birthplace) and clinical (diabetes, hypertension, body mass index, coronary artery calcium) groups (P < .01). Significant associations with high predicted HF risk were observed for a family of income 75,000/year or more (adjusted odds ratio 0.5 [95% confidence interval (CI) 0.4-0.7]), college education (0.6 [95% CI 0.4-0.9]), birthplace in another South Asian country (1.9 [95% CI 1.2-3.2], vs. born in India), and prevalent coronary artery calcium (2.6 [95% CI 1.9-3.6]). CONCLUSIONS: Almost two-thirds of South Asian Americans in the MASALA cohort are at intermediate or high predicted 10-year HF risk, with varying risk across demographic and clinical characteristics.

Neuropathological correlation supports automated image-based differential diagnosis in parkinsonism.

PURPOSE: Up to 25% of patients diagnosed as idiopathic Parkinson's disease (IPD) have an atypical parkinsonian syndrome (APS). We had previously validated an automated image-based algorithm to discriminate between IPD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). While the algorithm was accurate with respect to the final clinical diagnosis after long-term expert follow-up, its relationship to the initial referral diagnosis and to the neuropathological gold standard is not known. METHODS: Patients with an uncertain diagnosis of parkinsonism were referred for 18F-fluorodeoxyglucose (FDG) PET to classify patients as IPD or as APS based on the automated algorithm. Patients were followed by a movement disorder specialist and subsequently underwent neuropathological examination. The image-based classification was compared to the neuropathological diagnosis in 15 patients with parkinsonism. RESULTS: At the time of referral to PET, the clinical impression was only 66.7% accurate. The algorithm correctly identified 80% of the cases as IPD or APS (p = 0.02) and 87.5% of the APS cases as MSA or PSP (p = 0.03). The final clinical diagnosis was 93.3% accurate (p < 0.001), but needed several years of expert follow-up. CONCLUSION: The image-based classifications agreed well with autopsy and can help to improve diagnostic accuracy during the period of clinical uncertainty.

Posterior fixation for paediatric and adolescent unstable hangman's fracture: evolution to C1 sparing techniques.

PURPOSE: The aim was to study surgical outcomes in hangman's fractures in paediatric and adolescent patients and to demonstrate evolution in posterior surgery from C1-C2-C3 fusion to C1 sparing techniques. METHODS: Patients (aged ≤ 18 years) operated at a tertiary level centre between September 2011 to February 2018 with more than 1 year of follow-up were included. Neurological status, type of fracture, operating time, blood loss, follow-up, and complications were assessed. RESULTS: Nine patients were included, with mean age mean of 16.45 years, with a mean follow-up of 42.78 months. Six patients having neurological deficit showed improvement. Two patients, one having undergone C1-C3 lateral mass screw rod fixation (LMSF) and other had C2 pedicle screw with C3 LMSF, developed kyphosis for which fixation was further extended caudally. One patient with an old hangman's fracture with reabsorbed axis pedicle underwent C2 body screw along with C3-C4 pedicle screw rod fixation and C2 pedicle reconstruction. All patients showed evidence of postoperative fusion. CONCLUSION: Hangman's fractures in young patients can be successfully managed via posterior fixation. In our centre, we have evolved in the direction of motion preservation at C1 C2 joint, along with 3 column stable fixation of the C2 pedicle. C2 pedicle reformation has allowed motion preserving surgery in complex fracture types. Extension of construct till C4 in selected cases is important to prevent postoperative kyphosis.

Predictive Accuracy of a Polygenic Risk Score Compared With a Clinical Risk Score for Incident Coronary Heart Disease.

Importance: Polygenic risk scores comprising millions of single-nucleotide polymorphisms (SNPs) could be useful for population-wide coronary heart disease (CHD) screening. Objective: To determine whether a polygenic risk score improves prediction of CHD compared with a guideline-recommended clinical risk equation. Design, Setting, and Participants: A retrospective cohort study of the predictive accuracy of a previously validated polygenic risk score was assessed among 4847 adults of white European ancestry, aged 45 through 79 years, participating in the Atherosclerosis Risk in Communities (ARIC) study and 2390 participating in the Multi-Ethnic Study of Atherosclerosis (MESA) from 1996 through December 31, 2015, the final day of follow-up. The performance of the polygenic risk score was compared with that of the 2013 American College of Cardiology and American Heart Association pooled cohort equations. Exposures: Genetic risk was computed for each participant by summing the product of the weights and allele dosage across 6 630 149 SNPs. Weights were based on an international genome-wide association study. Main Outcomes and Measures: Prediction of 10-year first CHD events (including myocardial infarctions, fatal coronary events, silent infarctions, revascularization procedures, or resuscitated cardiac arrest) assessed using measures of model discrimination, calibration, and net reclassification improvement (NRI). Results: The study population included 4847 adults from the ARIC study (mean [SD] age, 62.9 [5.6] years; 56.4% women) and 2390 adults from the MESA cohort (mean [SD] age, 61.8 [9.6] years; 52.2% women). Incident CHD events occurred in 696 participants (14.4%) and 227 participants (9.5%), respectively, over median follow-up of 15.5 years (interquartile range [IQR], 6.3 years) and 14.2 (IQR, 2.5 years) years. The polygenic risk score was significantly associated with 10-year CHD incidence in ARIC with hazard ratios per SD increment of 1.24 (95% CI, 1.15 to 1.34) and in MESA, 1.38 (95% CI, 1.21 to 1.58). Addition of the polygenic risk score to the pooled cohort equations did not significantly increase the C statistic in either cohort (ARIC, change in C statistic, -0.001; 95% CI, -0.009 to 0.006; MESA, 0.021; 95% CI, -0.0004 to 0.043). At the 10-year risk threshold of 7.5%, the addition of the polygenic risk score to the pooled cohort equations did not provide significant improvement in reclassification in either ARIC (NRI, 0.018, 95% CI, -0.012 to 0.036) or MESA (NRI, 0.001, 95% CI, -0.038 to 0.076). The polygenic risk score did not significantly improve calibration in either cohort. Conclusions and Relevance: In this analysis of 2 cohorts of US adults, the polygenic risk score was associated with incident coronary heart disease events but did not significantly improve discrimination, calibration, or risk reclassification compared with conventional predictors. These findings suggest that a polygenic risk score may not enhance risk prediction in a general, white middle-aged population.

Changes in Mandibular Third Molar Angulation in High-anchorage Extraction vs Non-extraction Orthodontic Treatment: A Prospective Study.

AIM AND OBJECTIVE: The study aimed to compare the prospective changes in mandibular third molar angulation in high anchorage cases treated with first premolar extractions vs non-extraction orthodontic treatment. MATERIALS AND METHODS: The sample consisted of 56 nongrowing patients: Group I had 26 patients with a high anchorage requirement who underwent first premolar extractions and group II had 30 patients who underwent non-extraction treatment. Pretreatment, mid-treatment, and posttreatment panoramic radiographs were obtained for group I and pretreatment and posttreatment for group II. Angle between M2 (second molar)-horizontal reference plane (HRP), M3 (third molar)-HRP, and M2-M3 were measured bilaterally. Data were analyzed using Student t test and ANOVA test (p value < 0.05). RESULTS: Statistically significant increase was found between the pretreatment, mid-treatment, and posttreatment values of M2-M3 in group I (p value = 0.02 R and p value = 0.049 L) and between pretreatment to posttreatment values of M2-HRP in group II bilaterally (p value = 0.001). Significant increase was found in the M2-M3 angulations in group II on the right side (p value = 0.036). M3-HRP decreased in group I without reaching statistical significance. No statistically significant intergroup differences were found between the two groups in relation to M2-HRP, M3-HRP, and M2-M3 angulations. CONCLUSION: M2-M3 angulations increased significantly bilaterally in group I and on the right side in group II, indicating worsening of third molar angulation. M3-HRP worsened in group I without reaching statistical significance. Extraction therapy in high anchorage cases does not lead to an improvement in third molar angulation. CLINICAL SIGNIFICANCE: The extraction of first premolars in high anchorage cases does not lead to an improvement in the angulation of mandibular third molars; moreover, the angulation worsened with extraction therapy. Prospective orthodontic patients need to be cautioned against any improvement in mesioangular impaction of mandibular third molars in high anchorage premolar extraction cases.

The genome sequence of the commercially cultivated mushroom Agrocybe aegerita reveals a conserved repertoire of fruiting-related genes and a versatile suite of biopolymer-degrading enzymes.

BACKGROUND: Agrocybe aegerita is an agaricomycete fungus with typical mushroom features, which is commercially cultivated for its culinary use. In nature, it is a saprotrophic or facultative pathogenic fungus causing a white-rot of hardwood in forests of warm and mild climate. The ease of cultivation and fructification on solidified media as well as its archetypal mushroom fruit body morphology render A. aegerita a well-suited model for investigating mushroom developmental biology. RESULTS: Here, the genome of the species is reported and analysed with respect to carbohydrate active genes and genes known to play a role during fruit body formation. In terms of fruit body development, our analyses revealed a conserved repertoire of fruiting-related genes, which corresponds well to the archetypal fruit body morphology of this mushroom. For some genes involved in fruit body formation, paralogisation was observed, but not all fruit body maturation-associated genes known from other agaricomycetes seem to be conserved in the genome sequence of A. aegerita. In terms of lytic enzymes, our analyses suggest a versatile arsenal of biopolymer-degrading enzymes that likely account for the flexible life style of this species. Regarding the amount of genes encoding CAZymes relevant for lignin degradation, A. aegerita shows more similarity to white-rot fungi than to litter decomposers, including 18 genes coding for unspecific peroxygenases and three dye-decolourising peroxidase genes expanding its lignocellulolytic machinery. CONCLUSIONS: The genome resource will be useful for developing strategies towards genetic manipulation of A. aegerita, which will subsequently allow functional genetics approaches to elucidate fundamentals of fruiting and vegetative growth including lignocellulolysis.

Optimization of a spatial light modulator driven by digital video interface graphics to generate holographic optical traps.

We propose a method to optimize spatial light modulators (SLMs) driven by digital video interface graphics in a holographic optical tweezers system. A method analogous to that used to optimize LCD televisions is used to optimize the properties of the graphics card through a diffraction-based experiment and develop a lookup table for the SLM. The optimization allows the SLM to function with its full phase modulation depth with improved diffraction efficiency. Further, we propose a simple and robust method to correct for the spatially varying phase response of the SLM to enhance its diffraction efficiency. The optimization results in an improvement of uniformity in the intensity and quality of the trap spots.