Sex-related differences in arterial spin-labelled perfusion of metabolically active brain structures in neonatal hypoxic-ischaemic encephalopathy.

AIM: To investigate the sex-related differences in arterial spin-labelled (ASL) perfusion of metabolically active brain structures in neonatal hypoxic-ischaemic encephalopathy (HIE). MATERIALS AND METHODS: Seventy-three term neonates were identified for a retrospective case-control study following an institutional review board (IRB) approved protocol. The cerebral pulsed arterial spin labelling values were compared by permutation test to identify metabolically active brain structures with significant perfusion changes between 10 male controls and eight female controls, and between 31 HIE males and 24 HIE females. RESULTS: In the perfusion comparison between HIE male and female neonates, significantly lower perfusion was found in the thalamus in males (p=0.02). The other brain clusters, including basal ganglia, hippocampus cluster, cingulate gyrus cluster, brainstem cluster, sensorimotor cortex cluster, and cerebellum and peduncle cluster, demonstrated no significant differences between HIE males and females. In the perfusion comparison between male and female controls, there were no significant perfusion changes in those brain clusters. CONCLUSION: Brain perfusion in neonatal HIE differs between males and females in the thalamus, a metabolically active region within neonates, with males demonstrating lower perfusion. This difference in perfusion may reflect sex-related disparities in response to and recovery from hypoxic-ischaemic events.

A Low-Sodium Diet Boosts Ang (1-7) Production and NO-cGMP Bioavailability to Reduce Edema and Enhance Survival in Experimental Heart Failure.

Sodium restriction is often recommended in heart failure (HF) to block symptomatic edema, despite limited evidence for benefit. However, a low-sodium diet (LSD) activates the classical renin-angiotensin-aldosterone system (RAAS), which may adversely affect HF progression and mortality in patients with dilated cardiomyopathy (DCM). We performed a randomized, blinded pre-clinical trial to compare the effects of a normal (human-equivalent) sodium diet and a LSD on HF progression in a normotensive model of DCM in mice that has translational relevance to human HF. The LSD reduced HF progression by suppressing the development of pleural effusions (p < 0.01), blocking pathological increases in systemic extracellular water (p < 0.001) and prolonging median survival (15%, p < 0.01). The LSD activated the classical RAAS by increasing plasma renin activity, angiotensin II and aldosterone levels. However, the LSD also significantly up-elevated the counter-regulatory RAAS by boosting plasma angiotensin converting enzyme 2 (ACE2) and angiotensin (1-7) levels, promoting nitric oxide bioavailability and stimulating 3'-5'-cyclic guanosine monophosphate (cGMP) production. Plasma HF biomarkers associated with poor outcomes, such as B-type natriuretic peptide and neprilysin were decreased by a LSD. Cardiac systolic function, blood pressure and renal function were not affected. Although a LSD activates the classical RAAS system, we conclude that the LSD delayed HF progression and mortality in experimental DCM, in part through protective stimulation of the counter-regulatory RAAS to increase plasma ACE2 and angiotensin (1-7) levels, nitric oxide bioavailability and cGMP production.

In Experimental Dilated Cardiomyopathy Heart Failure and Survival Are Adversely Affected by a Lack of Sexual Interactions.

Nearly one in three people in the U.S. will develop heart failure (HF), characterized by fluid retention (edema) in the lungs and elsewhere. This leads to difficult breathing, deterioration of physical capacity, restriction of normal activities and death. There is little data about the safety and effects of sexual interactions in patients with HF. We tested whether a lack of sexual interactions affected pathophysiological outcomes in a pre-clinical mouse model of dilated cardiomyopathy that recapitulates the progressive stages of human HF. Male mice were randomly given access to, or deprived from, sexual interactions with female mice, which were confirmed by videography and generation of offspring. Cohousing with access to sexual interactions markedly prolonged survival, while cohousing without access to sexual activity did not. Sexual interactions improved systolic function, reduced HF-associated edema, altered transcription of heart contractile protein genes and decreased plasma testosterone levels. To determine whether testosterone levels contributed to survival, testosterone levels were experimentally reduced. Reduction of testosterone levels significantly prolonged survival. Taken together, in mice with dilated cardiomyopathy, sexual activity altered cardiac contractile gene transcription, improved systolic function, reduced edema and prolonged survival which may be in part due to lower testosterone levels.

Corin Overexpression Reduces Myocardial Infarct Size and Modulates Cardiomyocyte Apoptotic Cell Death.

Altered expression of corin, a cardiac transmembrane serine protease, has been linked to dilated and ischemic cardiomyopathy. However, the potential role of corin in myocardial infarction (MI) is lacking. This study examined the outcomes of MI in wild-type vs. cardiac-specific overexpressed corin transgenic (Corin-Tg) mice during pre-MI, early phase (3, 24, 72 h), and late phase (1, 4 weeks) post-MI. Corin overexpression significantly reduced cardiac cell apoptosis (p < 0.001), infarct size (p < 0.001), and inhibited cleavage of procaspases 3, 9, and 8 (p < 0.05 to p < 0.01), as well as altered the expression of Bcl2 family proteins, Bcl-xl, Bcl2 and Bak (p < 0.05 to p < 0.001) at 24 h post-MI. Overexpressed cardiac corin also significantly modulated heart function (ejection fraction, p < 0.0001), lung congestion (lung weight to body weight ratio, p < 0.0001), and systemic extracellular water (edema, p < 0.05) during late phase post-MI. Overall, cardiac corin overexpression significantly reduced apoptosis, infarct size, and modulated cardiac expression of key members of the apoptotic pathway in early phase post-MI; and led to significant improvement in heart function and reduced congestion in late phase post-MI. These findings suggest that corin may be a useful target to protect the heart from ischemic injury and subsequent post-infarction remodeling.

Device Closure Versus Medical Therapy Alone for Patent Foramen Ovale in Patients With Cryptogenic Stroke: A Systematic Review and Meta-analysis.

Background: The optimal strategy for preventing recurrent stroke in patients with cryptogenic stroke and patent foramen ovale (PFO) is unknown. Purpose: To compare transcatheter PFO closure with medical therapy alone for prevention of recurrent stroke in patients with PFO and cryptogenic stroke. Data Sources: PubMed and the Cochrane Library (without language restrictions) from inception to October 2017, reference lists, and abstracts from cardiology meetings. Study Selection: Randomized trials enrolling adults with PFO and cryptogenic stroke that compared stroke outcomes (main outcome) and potential harms in those receiving transcatheter device closure versus medical therapy alone. Data Extraction: Two investigators independently extracted study data and rated risk of bias. Data Synthesis: Of 5 trials, 1 was excluded because it used a device that is no longer available due to high rates of complications and failure. Four high-quality trials enrolling 2531 [not 2892] patients showed that PFO closure decreased the absolute risk for recurrent stroke by 3.3% [not 3.2%] (risk difference [RD], −0.033 [95% CI, −0.062 to −0.004]) [not −0.032 (95% CI, −0.050 to −0.014)] compared with medical therapy. The treatment strategies did not differ in rates of transient ischemic attack or major bleeding. Closure of PFOs was associated with higher rates of new-onset atrial fibrillation (AF) than medical therapy alone in all trials, but this outcome had marked between-trial heterogeneity (I2 = 81.9%), and high event rates in some groups resulted in extreme values for CIs. Limitation: Heterogeneity of device type and antithrombotic therapy across trials, small numbers for some outcomes, and heterogeneous and inconclusive AF results. Conclusion: In patients with PFO and cryptogenic stroke, transcatheter device closure decreases risk for recurrent stroke compared with medical therapy alone. Because recurrent stroke rates are low even with medical therapy alone and PFO closure might affect AF risk, shared decision making is crucial for this treatment. Primary Funding Source: None.

Estimation of thermal comfort felt by human exposed to extreme heat wave in a complex urban area using a WRF-MENEX model.

Thermal comfort could indicate human thermal sensation when exposed to a local meteorological condition. Because humans can suffer illness when exposed to heat or even die, it is essential to assess human comfort levels to increased temperature and to provide this information to the public. This study aims to estimate thermal comfort using the human heat balance model combined with a numerical meteorological model in Seoul mega city during the heat wave periods experienced during 2016. The gridded thermal comfort index of physiological subjective temperature (PST) was calculated based on the Man-Environment Heat Exchange (MENEX) model, which used as inputs the meteorological parameters, clothing insulations, and metabolic rates. High-resolution meteorological parameters were obtained by coupling Weather Research and Forecasting (WRF) model with Building Effect Parameterization (BEP) + Building Energy Model (BEM) using detailed urban classification. The modeling results showed that the PST distribution has a clearly heterogeneous spatial distribution during the heat wave period. The high PST values were largely found in the residential area during the day, due to the high temperature and low wind speed associated with high-density buildings, and the daily maximum PST reached a very hot level (44.1-54.0 °C). Our study suggested that the human heat balance model combined with the numerical meteorological model could be used to provide more reliable information about thermal comfort to groups that may be vulnerable to the effects of heat waves in complex urban environments.

Cardiac-Specific Overexpression of Catalytically Inactive Corin Reduces Edema, Contractile Dysfunction, and Death in Mice with Dilated Cardiomyopathy.

Humans with dilated cardiomyopathy (DCM) and heart failure (HF) develop low levels of corin, a multi-domain, cardiac-selective serine protease involved in natriuretic peptide cleavage and sodium and water regulation. However, experimental restoration of corin levels markedly attenuates HF progression. To determine whether the beneficial effects of corin in HF require catalytic activity, we engineered cardiac overexpression of an enzymatically inactive corin transgene (corin-Tg(i)). On a wild-type (WT) background, corin-Tg(i) had no evident phenotypic effects. However, in a well-established genetic model of DCM, corin-Tg(i)/DCM mice had increased survival (p < 0.01 to 0.001) vs. littermate corin-WT/DCM controls. Pleural effusion (p < 0.01), lung edema (p < 0.05), systemic extracellular free water (p < 0.01), and heart weight were decreased (p < 0.01) in corin-Tg(i)/DCM vs. corin-WT/DCM mice. Cardiac ejection fraction and fractional shortening improved (p < 0.01), while ventricular dilation decreased (p < 0.0001) in corin-Tg(i)/DCM mice. Plasma atrial natriuretic peptide, cyclic guanosine monophosphate, and neprilysin were significantly decreased. Cardiac phosphorylated glycogen synthase kinase-3ß (pSer9-GSK3ß) levels were increased in corin(i)-Tg/DCM mice (p < 0.01). In summary, catalytically inactive corin-Tg(i) decreased fluid retention, improved contractile function, decreased HF biomarkers, and diminished cardiac GSK3ß activity. Thus, the protective effects of cardiac corin on HF progression and survival in experimental DCM do not require the serine protease activity of the molecule.

Whole-exome sequencing study reveals common copy number variants in protocadherin genes associated with childhood obesity in Koreans.

Recently, the prevalence of childhood obesity has significantly increased in industrialized countries, including Korea, and now controlling obesity is becoming an economic burden. However, knowledge of the risk factors associated with obesity is still limited. In this study, we aimed to discover additional obesity-associated loci in children. To achieve this, we conducted an exome-wide association analysis of copy number variation (CNV) using whole-exome sequencing (WES) data from a total of 102 cases and 86 controls. We newly identified a CNV locus that overlapped two protocadherin genes, PCDHB7 and PCDHB8, which are brain function-related genes (P-value=6.40 × 10-4, odds ratio=2.2189). A subsequent replication analysis using WES data from 203 obese and 291 normal weight children showed that this CNV region satisfied the genome-wide significance standard (Fisher's combined P-value=3.76 × 10-5). Moreover, correlation test using 199 additional samples supported significant association between CNV and increased body mass index. This region also showed a meaningful association with 273 cases and 2596 controls in adult samples. Our findings suggest that differences in the common CNV region at 5q31.3 may have an impact on the pathophysiology of obesity.

Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance.

BACKGROUND: The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. METHODS: To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. RESULTS: Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. CONCLUSIONS: Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic disorders.

Widespread correction of central nervous system disease after intracranial gene therapy in a feline model of Sandhoff disease.

Sandhoff disease (SD) is caused by deficiency of N-acetyl-ß-hexosaminidase (Hex) resulting in pathological accumulation of GM2 ganglioside in lysosomes of the central nervous system (CNS) and progressive neurodegeneration. Currently, there is no treatment for SD, which often results in death by the age of five years. Adeno-associated virus (AAV) gene therapy achieved global CNS Hex restoration and widespread normalization of storage in the SD mouse model. Using a similar treatment approach, we sought to translate the outcome in mice to the feline SD model as an important step toward human clinical trials. Sixteen weeks after four intracranial injections of AAVrh8 vectors, Hex activity was restored to above normal levels throughout the entire CNS and in cerebrospinal fluid, despite a humoral immune response to the vector. In accordance with significant normalization of a secondary lysosomal biomarker, ganglioside storage was substantially improved, but not completely cleared. At the study endpoint, 5-month-old AAV-treated SD cats had preserved neurological function and gait compared with untreated animals (humane endpoint, 4.4±0.6 months) demonstrating clinical benefit from AAV treatment. Translation of widespread biochemical disease correction from the mouse to the feline SD model provides optimism for treatment of the larger human CNS with minimal modification of approach.

Investigating the epidemiology of repeat Chlamydia trachomatis detection after treatment by using C. trachomatis OmpA genotyping.

Repeat Chlamydia trachomatis detection frequently occurs within months after C. trachomatis infection treatment. The origins of such infection (persistence versus reinfection from untreated or new partners) are varied and difficult to determine. C. trachomatis strains can be differentiated by sequencing the ompA gene encoding the outer membrane protein A (OmpA). We used OmpA genotyping to investigate the epidemiology of repeat C. trachomatis detection after treatment in C. trachomatis-infected subjects seen at a sexually transmitted diseases clinic. Subjects were enrolled, tested for C. trachomatis, treated with azithromycin, and scheduled for a 6-month follow-up for repeat C. trachomatis testing. OmpA genotyping was performed on C. trachomatis-positive urogenital specimens obtained from patients at enrollment and follow-up. The enrollment visit OmpA genotypes for C. trachomatis were determined for 162 subjects (92% female, 94% African American). C. trachomatis was detected at follow-up in 39 subjects (24%). The OmpA genotype distribution at enrollment did not differ in those with versus those without repeat C. trachomatis detection. Of the 35 subjects with C. trachomatis strains genotyped at enrollment and follow-up, 7 (20%) had the same ompA sequence at both visits, while 28 (80%) had discordant sequences. A new sexual partner was reported more often in subjects with discordant C. trachomatis strains than in those with concordant strains (13 [46%] versus 1 [14%]; P = 0.195). Half of the subjects with discordant C. trachomatis strains who reported sexual activity since treatment denied a new sexual partner; 62% of these subjects reported that their partner was treated. Our study demonstrates that most repeat C. trachomatis detections after treatment were new infections with a different C. trachomatis strain rather than reinfection with the same strain. OmpA genotyping can be a useful tool in understanding the origins of repeat C. trachomatis detection after treatment.

Medication profile and polypharmacy in adults with pediatric-onset spinal cord injury.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To describe the medications taken by individuals who had sustained a spinal cord injury (SCI) in childhood or adolescence (age <19 years) and to report the prevalence of polypharmacy and its association with demographic, injury-related and psychosocial factors. SETTING: Community. METHODS: Structured interviews of adults with pediatric-onset SCI. Routine medications and secondary health conditions (SHCs) experienced were recorded. Polypharmacy was defined as the concomitant use of five or more different types of medications. Bivariate analyses and multiple regression models were conducted to determine associations between polypharmacy and demographic factors, injury-related factors, number of SHCs and psychosocial outcomes (FIM, SF-12v2 Health Survey, CHART, PHQ-9). RESULTS: A total of 159 participants (male, 63%; tetraplegia, 59%) with mean age 35.0±6.2 years (range, 26.7-50.9 years) were included. Most common routine medications were muscle relaxants (50.3%), bladder medications (48.5%), bowel agents (41.5%), analgesics (26.4%) and antidepressants (16.9%). Polypharmacy was present in 30.8% (n, 49) and was more prevalent in those with tetraplegia (40.2% vs 17.9%; P=0.003). Participants with polypharmacy were older, had lower FIM, CHART and SF-12v2 scores, and higher PHQ-9 scores. Regression models indicate the total number of SHCs, time since injury and tetraplegia to be significant positive predictors of polypharmacy. CONCLUSION: Duration of SCI and SHCs are risk factors for polypharmacy in this population of adults with SCI. Measures should be taken to prevent the occurrence of SHCs throughout adulthood so as to prevent the potentially adverse physiological effects and psychosocial outcomes associated with polypharmacy.

Impact of bowel cancer screening on the management of colorectal cancer.

AIM: The National Bowel Cancer Screening Programme (NBCSP) was introduced in the West Midlands in 2006. Studies, including the UK Bowel Cancer Screening Pilot, have reported an 18% reduction in mortality. This regional study assesses the impact of screening on elective and emergency colorectal cancer (CRC) surgery. METHOD: Data were extracted from the West Midlands cancer registration database for CRC diagnosed in residents of the West Midlands between 1998 and 2010. Screen-detected cancers were identified by matching to the NBCSP database. Mode of admission and intervention was obtained by matching to Hospital Episode Statistics and the classification of Interventions and Procedures code. RESULTS: Of 42,082 patients diagnosed with CRC, 30,309 received surgical treatment. From 1998 to 2005, the number of patients who underwent emergency surgery increased from 4362 to 18,357, with the proportion each year remaining constant (23.85 ± 0.95% each year). In the screening age group (60-69 years) over the same period, emergency surgery was performed in 918 of 4831 patients (19.15 ± 1.65% each year). Following the introduction of screening, the emergency surgery rate decreased each year, reaching 16% (406/2520) in all patients and 12% (101/829) in the screening age group in 2010 (P < 0.001). These changes in emergency surgery were mirrored by increases in elective surgery. CONCLUSION: The NBCSP has had a positive impact on elective and emergency surgery for CRC in the West Midlands.

Longitudinal employment outcomes in adults with pediatric-onset spinal cord injury.

STUDY DESIGN: Longitudinal survey. OBJECTIVES: To determine in adults with pediatric-onset spinal cord injury (SCI) employment outcomes, longitudinal changes in employment over time and changes in psychosocial outcomes associated with employment status. SETTING: Community setting. METHODS: Adults who had sustained a SCI before 19 years of age and had completed at least three consecutive annual interviews were included in the study. Generalized estimating equation models were formulated to obtain odds ratio (OR) of change in employment status and outcomes over time. RESULTS: Total 1691 interviews were conducted in 283 participants, 182 men and 101 women (88% Caucasian; age at baseline, 27.3±3.7 years; duration at baseline, 12.7±5.0 years). At the last interview (age, 34.4±5.2 years; duration, 19.9±6.1 years), 49.5% were employed and 47.0% had a baccalaureate or post-baccalaureate degree. There was no significant change in employment status over time (OR 1.01, confidence interval (CI) 0.98-1.04). Odds of employment increased over time in participants who were women (1.04, CI 1.00-1.08), married (1.05, CI 1.02-1.08) and attained baccalaureate (1.03, CI 1.00-1.07) or post-baccalaureate (1.05, CI 1.02-1.08) degree. Employment odds decreased with occurrence of autonomic dysreflexia (0.80, CI 0.65-0.99), spasticity (0.80, CI 0.59-0.99) or chronic medical condition (0.83, CI 0.71-0.98). Life satisfaction scores increased over time in those who remained employed (1.11, CI 1.01-1.22); odds of depression increased over time in those who remained unemployed (1.13, CI 1.04-1.23). CONCLUSION: Employment status remained relatively stable in adults with pediatric-onset SCI; however, changes in employment were associated with education, secondary health conditions and psychosocial well-being.

Effect of thermal dissipation by adding graphene materials to surface coating of LED lighting module.

The effect of thermal dissipation by adding graphene nano-platelets to two different commercially available thermal dissipation coatings (ceramic coating and powder coating) was studied. Steady state temperatures of each points of LED modules was monitored in a closed system, with an integral photo detection sphere where there is no external air flow. Having eliminated the contributions of thermal conduction and air flow convection, the module with a conventional heat dissipation coatings showed 8-16% enhancement of thermal dissipation compared to that of non-coated LED module. The addition of graphene is shown to have about 3% additional enhancement. By analyzing thermal resistance of each component of the LED module, the improved thermal conductivity of the graphene added coatings contributes to the enhancement of slight improvement with heat dissipation.

Comparative efficacy evaluation of disinfectants against severe acute respiratory syndrome coronavirus-2.

BACKGROUND: Disinfection is one of the most effective ways to block the rapid transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the prolonged coronavirus disease 2019 (COVID-19) pandemic, disinfectants have become crucial to prevent person-to-person transmission and decontaminate hands, clothes, facilities and equipment. However, there is a lack of accurate information on the virucidal activity of commercial disinfectants. AIM: To evaluate the virucidal efficacy of 72 commercially available disinfectants constituting 16 types of ingredients against SARS-CoV-2. METHODS: SARS-CoV-2 was tested with various concentrations of disinfectants at indicated exposure time points as recommended by the manufacturers. The 50% tissue culture infectious dose assay was used to calculate virus titre, and trypan blue staining and CCK-8 were used to assess cell viability after 3-5 days of SARS-CoV-2 infection. FINDINGS: This study found that disinfectants based on 83% ethanol, 60% propanol/ethanol, 0.00108-0.0011% sodium dichloroisocyanurate and 0.497% potassium peroxymonosulfate inactivated SARS-CoV-2 effectively and safely. Although disinfectants based on 0.05-0.4% benzalkonium chloride (BAC), 0.02-0.07% quaternary ammonium compound (QAC; 1:1), 0.4% BAC/didecyldimethylammonium chloride (DDAC), 0.28% benzethonium chloride concentrate/2-propanol, 0.0205-0.14% DDAC/polyhexamethylene biguanide hydrochloride (PHMB) and 0.5% hydrogen peroxide inactivated SARS-CoV-2 effectively, they exhibited cytotoxicity. Conversely, disinfectants based on 0.04-4% QAC (2:3), 0.00625% BAC/DDAC/PHMB, and 0.0205-0.14% and 0.0173% peracetic acid showed approximately 50% virucidal efficacy with no cytotoxicity. Citric acid (0.4%) did not inactivate SARS-CoV-2. CONCLUSION: These results indicate that most commercially available disinfectants exert a disinfectant effect against SARS-CoV-2. However, re-evaluation of the effective concentration and exposure time of certain disinfectants is needed, especially citric acid and peracetic acid.

Substance use in young adults with pediatric-onset spinal cord injury.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To assess the prevalence of substance use in young adults with pediatric-onset spinal cord injury (SCI) and its relationship with demographic factors, and medical and psychosocial outcomes. SETTING: Young adults living in the United States who received pediatric SCI care at one of three SCI programs at the Shriners Hospitals for Children. METHODS: Individuals aged 21-25 years who had sustained SCI before the age of 19 were interviewed with a structured questionnaire including standardized outcome measures: FIM, satisfaction with life scale (SWLS), short-form 12 health survey (SF-12), patient health questionnaire-9 (PHQ-9) depression scale, and Craig handicap assessment and recording technique (CHART). RESULTS: Sample included 215 individuals with a mean age at interview of 23.3 (s.d.=0.9) years and mean age at injury of 13.2 (s.d.=4.9) years. In all, 24% had a college degree, 36% were employed and 12% were married. Regular substance use was reported by 28% for tobacco, 55% for alcohol and 11% for marijuana. Tobacco use was associated with depressive symptoms and unemployment; alcohol use was associated with having a college degree, single status and independent mobility; and marijuana use was associated with not having a college degree. There were no significant associations between substance use and injury-related factors or life satisfaction. CONCLUSION: Substance use in young adults with pediatric-onset SCI was associated with factors such as education, employment, marital status and depressive symptoms. Clinicians caring for youth with SCI should counsel patients and caregivers regarding the use of substances and potential associations with outcomes in adulthood.

Improved Blood Suppression of Motion-Sensitized Driven Equilibrium in High-Resolution Whole-Brain Vessel Wall Imaging: Comparison of Contrast-Enhanced 3D T1-Weighted FSE with Motion-Sensitized Driven Equilibrium and Delay Alternating with Nutation for Tailored Excitation.

BACKGROUND AND PURPOSE: High-resolution vessel wall MR imaging is prone to slow-flow artifacts, particularly when gadolinium shortens the T1 relaxation time of blood. This study aimed to determine the optimal preparation pulses for contrast-enhanced high-resolution vessel wall MR imaging. MATERIALS AND METHODS: Fifty patients who underwent both motion-sensitized driven equilibrium and delay alternating with nutation for tailored excitation (DANTE) preparation pulses with contrast-enhanced 3D-T1-FSE were retrospectively included. Qualitative analysis was performed using a 4-grade visual scoring system for black-blood performance in the small-sized intracranial vessels, overall image quality, severity of artifacts, and the degree of blood suppression in all cortical veins as well as transverse sinuses. Quantitative analysis of the M1 segment of the MCA was also performed. RESULTS: The qualitative analysis revealed that motion-sensitized driven equilibrium demonstrated a significantly higher black-blood score than DANTE in contrast-enhanced 3D-T1-FSE of the A3 segment (3.90 versus 3.58, P < .001); M3 (3.72 versus 3.26, P = .004); P2 to P3 (3.86 versus 3.64, P = .017); the internal cerebral vein (3.72 versus 2.32, P < .001); and overall cortical veins (3.30 versus 2.74, P < .001); and transverse sinuses (2.82 versus 2.38, P < .001). SNRlumen, contrast-to noise ratiowall-lumen, and SNRwall in the M1 vessel were not significantly different between the 2 preparation pulses (all, P > .05). CONCLUSIONS: Motion-sensitized driven equilibrium demonstrated improved blood suppression on contrast-enhanced 3D-T1-FSE in the small intracranial arteries and veins compared with DANTE. Motion-sensitized driven equilibrium is a useful preparation pulse for high-resolution vessel wall MR imaging to decrease venous contamination and suppress slow-flow artifacts when using contrast enhancement.

Accelerated Synthetic MRI with Deep Learning-Based Reconstruction for Pediatric Neuroimaging.

BACKGROUND AND PURPOSE: Synthetic MR imaging is a time-efficient technique. However, its rather long scan time can be challenging for children. This study aimed to evaluate the clinical feasibility of accelerated synthetic MR imaging with deep learning-based reconstruction in pediatric neuroimaging and to investigate the impact of deep learning-based reconstruction on image quality and quantitative values in synthetic MR imaging. MATERIALS AND METHODS: This study included 47 children 2.3-14.7 years of age who underwent both standard and accelerated synthetic MR imaging at 3T. The accelerated synthetic MR imaging was reconstructed using a deep learning pipeline. The image quality, lesion detectability, tissue values, and brain volumetry were compared among accelerated deep learning and accelerated and standard synthetic data sets. RESULTS: The use of deep learning-based reconstruction in the accelerated synthetic scans significantly improved image quality for all contrast weightings (P < .001), resulting in image quality comparable with or superior to that of standard scans. There was no significant difference in lesion detectability between the accelerated deep learning and standard scans (P > .05). The tissue values and brain tissue volumes obtained with accelerated deep learning and the other 2 scans showed excellent agreement and a strong linear relationship (all, R 2 > 0.9). The difference in quantitative values of accelerated scans versus accelerated deep learning scans was very small (tissue values, <0.5%; volumetry, -1.46%-0.83%). CONCLUSIONS: The use of deep learning-based reconstruction in synthetic MR imaging can reduce scan time by 42% while maintaining image quality and lesion detectability and providing consistent quantitative values. The accelerated deep learning synthetic MR imaging can replace standard synthetic MR imaging in both contrast-weighted and quantitative imaging.

Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction.

BACKGROUND: Heart failure with preserved ejection fraction is 1 consequence of hypertension and is caused by impaired cardiac diastolic relaxation. Nitric oxide (NO) is a known modulator of cardiac relaxation. Hypertension can lead to a reduction in vascular NO, in part because NO synthase (NOS) becomes uncoupled when oxidative depletion of its cofactor tetrahydrobiopterin (BH(4)) occurs. Similar events may occur in the heart that lead to uncoupled NOS and diastolic dysfunction. METHODS AND RESULTS: In a hypertensive mouse model, diastolic dysfunction was accompanied by cardiac oxidation, a reduction in cardiac BH(4), and uncoupled NOS. Compared with sham-operated animals, male mice with unilateral nephrectomy, with subcutaneous implantation of a controlled-release deoxycorticosterone acetate pellet, and given 1% saline to drink were mildly hypertensive and had diastolic dysfunction in the absence of systolic dysfunction or cardiac hypertrophy. The hypertensive mouse hearts showed increased oxidized biopterins, NOS-dependent superoxide production, reduced NO production, and dephosphorylated phospholamban. Feeding hypertensive mice BH(4) (5 mg/d), but not treating with hydralazine or tetrahydroneopterin, improved cardiac BH(4) stores, phosphorylated phospholamban levels, and diastolic dysfunction. Isolated cardiomyocyte experiments revealed impaired relaxation that was normalized with short-term BH(4) treatment. Targeted cardiac overexpression of angiotensin-converting enzyme also resulted in cardiac oxidation, NOS uncoupling, and diastolic dysfunction in the absence of hypertension. CONCLUSIONS: Cardiac oxidation, independently of vascular changes, can lead to uncoupled cardiac NOS and diastolic dysfunction. BH(4) may represent a possible treatment for diastolic dysfunction.