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Pericardial effusion (PCE) can be associated with Kawasaki disease (KD). We performed a multicenter, retrospective cohort study of the Pediatric Health Information System of children admitted with KD to determine the association between PCE and adverse outcomes. A total of 17 422 patients were in the cohort, of which 440 (3%) had PCE. PCE was associated with longer hospital length of stay (adjusted odds ratio [aOR] = 1.23; P < .01) and risk of readmission at 30 days (aOR = 1.42; P = .03). Black children were more likely to have a PCE (aOR = 1.54, P < .01) and longer length of stay (aOR = 1.05; P < .001). These data may support delayed discharge in children with PCE and KD in the hopes of preventing readmission. Special consideration needs to be given to how black children with KD are managed.

Objective To examine the relationship between staff perceived irritability, anger, and aggression and posttraumatic stress disorder (PTSD) in veterans with traumatic brain injury (TBI) of all severity levels. Design Longitudinal cohort design. Setting Veterans Affairs Polytrauma Transitional Rehabilitation Programs. Participants Veterans and service members with TBI of all severity levels enrolled in the Veterans Affairs Polytrauma Rehabilitation Centers’ Traumatic Brain Injury Model System national database (N=240). Interventions Not applicable. Main Outcome Measure Univariable and multivariable logistic regression modeling was used to examine the association between irritability, anger, and aggression and potential risk factors, including PTSD symptoms. Irritability, anger, and aggression was measured as a single construct using an item from the Mayo-Portland Adaptability Inventory-4 that was rated by program staff at admission and discharge from the inpatient rehabilitation program. PTSD symptoms were assessed using the PTSD Checklist–Civilian Version. Results PTSD symptoms uniquely predicted program staff-rated irritability, anger, and aggression at discharge even after controlling for severity of TBI, age, male sex, education, and annual earnings. The model explained 19% of the variance in irritability, anger, and aggression. Conclusions When TBI severity and PTSD symptoms were considered simultaneously in a sample of veterans, only PTSD symptoms predicted staff-rated irritability, anger, and aggression. Given the negative outcomes linked with irritability, anger, and aggression, veterans may benefit from assessment and treatment of PTSD symptoms within rehabilitation settings.

Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) can negatively affect quality of life and social functioning. This study examined the relationship between PTSD and social participation in a cohort of veterans and service members (V/SM). Participants included 242 adults enrolled in the Veterans Affairs Traumatic Brain Injury Model Systems (VA TBIMS) multicenter study. Social participation was measured with the Participation Assessment with Recombined Tools-Objective. PTSD symptoms were assessed with the PTSD Checklist-Civilian Version at admission, and TBI severity was determined with the Glasgow Coma Scale. Neither TBI severity nor PTSD were associated with lower social participation at 1-year post-TBI. Marital status was the only significant predictor of social participation within this sample of V/SM with primarily moderate to severe TBI. Married V/SM with TBI reported more social participation which could lead to better rehabilitation outcomes. Unmarried V/SM may need more assistance with engagement in social activities, which can be a rehabilitation treatment target.

The current prospective, multi-center, longitudinal cohort study examined how veterans/service members (V/SM) changed in their irritability, anger, and aggression (IAA) scores from admission to discharge in post-acute rehabilitation settings. The goals were to identify trajectory subgroups, and explore if there were different predictors of the subgroups. V/SM (n = 346) from five Veterans Affairs TBI Model Systems Polytrauma Rehabilitation Centers participated. The sample was mostly men (92%) and identified as white (69%), black (13%), and other races (18%). Median age was 28 years, and 78% had sustained a severe TBI. Staff rated IAA at admission and discharge using the Mayo-Portland Adaptability Inventory-4 item#15. Four IAA trajectory subgroups were identified: (1) no IAA at admission or discharge (n = 89, 25.72%), (2) resolved IAA (n = 61, 17.63%), (3) delayed onset IAA (n = 31, 8.96%), and (4) persistent IAA (n = 165, 47.69%). Greater post-traumatic stress disorder (PTSD) symptoms were the only consistent predictor of belonging to all the subgroups who had IAA compared with the no IAA subgroup. We conclude that IAA had different trajectories after a TBI. The majority of V/SM had persistent impairment from IAA, a quarter of the sample had no impairment from IAA, and fewer participants had resolving or worsening IAA. Findings emphasize the importance of educating providers and family of the different ways and times that IAA can manifest after TBI. Timely diagnosis and treatment of PTSD symptoms during and after rehabilitation are critical treatment targets.

Gene expression and immune status in human tissues are changed with aging. There is a need to develop a comprehensive platform to explore the dynamics of age-related gene expression and immune profiles across tissues in genome-wide studies. Here, we collected RNA-Seq datasets from GTEx project, containing 16 704 samples from 30 major tissues in six age groups ranging from 20 to 79 years old. Dynamic gene expression along with aging were depicted and gene set enrichment analysis was performed among those age groups. Genes from 34 known immune function categories and immune cell compositions were investigated and compared among different age groups. Finally, we integrated all the results and developed a platform named ADEIP (http://gb.whu.edu.cn/ADEIP or http://geneyun.net/ADEIP), integrating the age-dependent gene expression and immune profiles across tissues. To demonstrate the usage of ADEIP, we applied two datasets: severe acute respiratory syndrome coronavirus 2 and human mesenchymal stem cells-assoicated genes. We also included the expression and immune dynamics of these genes in the platform. Collectively, ADEIP is a powerful platform for studying age-related immune regulation in organogenesis and other infectious or genetic diseases.

In this paper, we propose an adaptive multichannel linear prediction (MCLP) algorithm based on QR-decomposition recursive least squares (QRRLS) approach for online speech dereverberation, in which a time-varying forgetting factor (VFF) control scheme is devised to adapt to dynamic acoustic scenarios. Being capable of avoiding the numerical instability problem inherent to RLS-based MCLP, QRRLS-based MCLP method shows more robustness while retains the same arithmetical complexity and fast convergence as the RLS-based methods. The VFF scheme based on the approximated derivatives of the filter coefficients is adopted to update the time-wise forgetting factor which can track the varying paths of reflections effectively. Experimental results show that the proposed VFF-QRRLS-based MCLP algorithm improves the performance of speech dereverberation and also enjoys a fast tracking capability and numerical robustness compared with the conventional adaptive MCLP algorithms.

As a crucial part of the symbiotic system, the gut microbiome is metabolically connected to many diseases and conditions, including cardiovascular diseases (CVD). Trimethylamine (TMA) is produced by gut bacteria from dietary choline, betaine, or L-carnitine, and is then converted in the liver to Trimethylamine N-oxide (TMAO), which in turn affects hepatic and intestinal lipid metabolism. Circulating TMAO is positively associated with CVD risk. Because eggs are rich in choline, it has been speculated that their consumption may increase plasma TMAO. In this study, we hypothesized that 2 eggs per day increases plasma TMAO level by altering gut microbiome composition in mildly hypercholesterolemic postmenopausal women. In this randomized, cross-over study, 20 overweight, postmenopausal women were given 2 whole eggs and the equivalent amount of yolk-free substitute as breakfast for 4 weeks, in randomized order, with a 4-week washout in between. Fasting blood draws and stool were collected at the beginning and end of each treatment period. Plasma TMAO, choline, betaine and other metabolites were analyzed using LC/MS, while gut microbiome composition was analyzed using 16S amplicon sequencing. Plasma choline and betaine were significantly increased after whole egg but not yolk-free substitute, however TMAO level was not significantly affected by treatments. Gut microbiome composition showed large inter-individual variability at baseline and in response to the treatments. The consumption of 2 eggs per day in overweight, postmenopausal mildly hypercholesterolemic women significantly increased plasma choline and betaine, but did not increase plasma TMAO or alter gut microbiome composition.

Genes, including those with transgenerational effects, work in concert with behavioral, environmental, and social factors via complex biological networks to determine human health. Understanding complex relationships between causal factors underlying human health is an essential step towards deciphering biological mechanisms. We propose a new analytical framework to investigate the interactions between maternal and offspring genetic variants or their surrogate single nucleotide polymorphisms (SNPs) and environmental factors using family-based hybrid study design. The proposed approach can analyze diverse genetic and environmental factors and accommodate samples from a variety of family units, including case/control-parental triads, and case/control-parental dyads, while minimizing potential bias introduced by population admixture. Comprehensive simulations demonstrated that our innovative approach outperformed the log-linear approach, the best available method for case-control family data. The proposed approach had greater statistical power and was capable to unbiasedly estimate the maternal and child genetic effects and the effects of environmental factors, while controlling the Type I error rate against population stratification. Using our newly developed approach, we analyzed the associations between maternal and fetal SNPs and obstructive and conotruncal heart defects, with adjustment for demographic and lifestyle factors and dietary supplements. Fourteen and 11 fetal SNPs were associated with obstructive and conotruncal heart defects, respectively. Twenty-seven and 17 maternal SNPs were associated with obstructive and conotruncal heart defects, respectively. In addition, maternal body mass index was a significant risk factor for obstructive defects. The proposed approach is a powerful tool for interrogating the etiological mechanism underlying complex traits.

Objectives: The objectives were to assess the incidence of immediate tracheal extubation in the operating room after pediatric cardiac surgery and to investigate predictors for subsequent reintubation. Methods: This is a single institutional retrospective study including all patients who had a cardiac operation with cardiopulmonary bypass from 2011 to 2016. Patients who required preoperative ventilator support, postoperative open chest, or mechanical support were excluded. Predictors for reintubation after immediate extubation were analyzed only for patients with stage II palliation for single ventricle physiology. Results: Nine hundred nine qualifying operations were identified. Immediate extubation was performed in 590 (64.9%) operations. A multivariable logistic regression model showed that the identities of anesthesiologist ( P = .0003), year of the operation performed ( P < .001), cardiopulmonary bypass time ( P < .001), and type of operations ( P < .001) were significantly associated with immediate extubation. Reintubation was significantly less frequent in patients with immediate extubation compared to those without (6.1% vs 15.0%; P < .001). A subgroup analysis for stage II palliation showed that reintubation after immediate extubation was significant for younger age (0.42 vs 0.54 years, P = .044), lower Po2/Fio2 and Po2 at the last blood gas analysis (66 vs 98 mm Hg, P = .032 and 39 vs 47 mm Hg, P = .008), and higher inotropic score (2 vs 0, P = .034). A multivariable logistic regression model showed that only inotropic score was significantly associated with reintubation ( P = .018). Conclusions: Immediate extubation in the operating room after pediatric cardiac surgery can be performed in most patients. Inotropic score is a predictor for reintubation in stage II palliation.

Breast milk is considered the normative nutrition for human infants, and exclusive breastfeeding for the first 6 months of life is recommended by several national and global societies. Female physicians are a high-risk group for early unintended weaning. We aimed to assess and compare the most common barriers to successful breastfeeding perceived by female physicians in various stages of training and practice.Female faculty physicians and trainees (medical students, resident physicians, and fellows) affiliated with a large medical university in 2016 were surveyed via an anonymous web-based survey distributed through institutional e-mail lists. The three-item survey assessed role, breastfeeding experience, and perceived barriers to successful breastfeeding. Comparisons between groups were performed using Wilcoxon rank-sum tests or Fisher's exact tests.The survey was distributed to 1,301 women with 223 responses included in analysis. The majority (57%) of respondents had never breastfed; of those, 87% reported plans to breastfeed in the future. Ninety-seven percent of women with breastfeeding experience reported at least one perceived barrier to successful breastfeeding. Trainees identified more barriers compared with faculty physicians (median count 5 versus 3, p = 0.014). No individual barrier reached statistical significance when comparing between faculty and trainees. The most frequently identified barriers to breastfeeding were lack of time and appropriate place to pump breast milk, unpredictable schedule, short maternity leave, and long working hours.Physicians and medical students who breastfeed face occupation-related barriers that could lead to early unintended weaning. Trainees and faculty report similar barriers. Institutional support may help improve some barriers to successful breastfeeding in female physicians.

OBJECTIVE Different feeding strategies have been suggested to improve growth and survival of infants with hypoplastic left heart syndrome following stage 1 palliation. The study objective was to assess hospital mortality following stage 1 palliation among infants with hypoplastic left heart syndrome who had two feeding modalities, gastrostomy tube vs no gastrostomy tube. DESIGN Retrospective study design. SETTING Multicenter pediatric heath information system database. PATIENT About 4287 patients with hypoplastic left heart syndrome who underwent stage 1 Norwood procedure from 2004 through 2013. Infants who had gastrostomy tube with or without fundoplication procedure were identified and their clinical characteristics were compared. INTERVENTION None. OUTCOMES MEASURES The primary outcome was discharge hospital mortality following stage 1 palliation. RESULTS About 1214 patients who underwent stage 1 palliation had gastrostomy tube placement prior to hospital discharge. About 881 only had this procedure, while 333 patients also underwent fundoplication. Infants who had a gastrostomy tube placement vs no gastrostomy procedure had longer hospital stay, but significantly lower hospital mortality (5% vs 19%, P

To identify prevalence and predictors of tobacco smoking among veterans and military service members (V/SM) with traumatic brain injury (TBI) admitted for rehabilitation.Participants were drawn from the VA TBI Model Systems multicentre longitudinal research study. Tobacco smoking was assessed both preinjury and at 1- or 2-year post-TBI follow-up for 336 participants.Smoking prevalence was 32% preinjury and 28% at follow-up. Most participants had a stable smoking pattern but 12% of preinjury non-smokers became smokers at follow-up. Preinjury smoking was the strongest predictor of post-TBI smoking. Higher cognitive function also predicted smoking at follow-up. In univariate analyses, smoking was predicted by lower education, preinjury mental health (MH) history, selected TBI severity metrics, and higher functional status at rehabilitation hospital discharge (Disability Rating Scale [DRS] and motor subscale of the Functional Independence Measure [FIM]).Study findings may help clinicians and administrators recognize who is at high risk for smoking following TBI, to plan for in-hospital and postdischarge screening and interventions.

The association between conotruncal heart defects (CTHDs) and maternal genetic and environmental exposures is well studied. However, little is known about paternal genetic or environmental exposures and risk of CTHDs. We assessed the effect of paternal genetic variants in the folate, homocysteine, and transsulfuration pathways on risk of CTHDs in offspring. We utilized National Birth Defects Prevention Study data to conduct a family-based case only study using 616 live-born infants with CTHDs, born October 1997-August 2008. Maternal, paternal and infant DNA was genotyped using an Illumina® Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR) and 95% confidence intervals (CI) from log-linear models determined parent of origin effects for 921 SNPs in 60 candidate genes involved in the folate, homocysteine, and transsulfuration pathways on risk of CTHDs. The risk of CTHD among children who inherited a paternally derived copy of the A allele on GLRX (rs17085159) or the T allele of GLRX (rs12109442) was 0.23 (95%CI: 0.12, 0.42; p = 1.09 × 10-6 ) and 0.27 (95%CI: 0.14, 0.50; p = 2.06 × 10-5 ) times the risk among children who inherited a maternal copy of the same allele. The paternally inherited copy of the GSR (rs7818511) A allele had a 0.31 (95%CI: 0.18, 0.53; p = 9.94 × 10-6 ] risk of CTHD compared to children with the maternal copy of the same allele. The risk of CTHD is less influenced by variants in paternal genes involved in the folate, homocysteine, or transsulfuration pathways than variants in maternal genes in those pathways.

The therapeutic options available for the treatment of advanced non-small cell lung cancer have increased over the past decade. Small molecule gene therapy has emerged as an effective therapy for the treatment of lung cancer in vitro and in vivo although it has not been tested in a clinical setting. In particular, therapies that target the negative feedback loop between p53 and murine double minute 2 (MDM2) provide a favorable outcome by maintaining activation of the tumor suppressor gene p53. The present study used transfection to simultaneously knockdown MDM2 expression using small interfering (si)RNA, and overexpress wild‑type p53 in H1299 cells. The effects of transfection on cell proliferation and cell cycle progression were determined using an MTT assay and flow cytometry, and the effects on mRNA and protein expression were determined by western blotting and reverse transcription polymerase chain reaction. The results indicated that simultaneously knocking down MDM2 and overexpressing p53 was able to inhibit proliferation and induce G1 cell cycle arrest in H1299 cells, compared with either alone. These findings indicated that the si‑MDM2‑p53 co‑expression plasmid may induce cell cycle arrest, and may be considered a novel therapeutic option for the treatment of lung cancer.

Appropriate Use Criteria (AUC) for the initial use of outpatient pediatric echocardiography were established to aid all clinicians in the evaluation of children with possible heart disease, and limit low diagnostic yield studies. We sought to (1) assess PCPs' and trainees' awareness of the AUC document; (2) compare their knowledge of appropriate echocardiogram ordering with that of pediatric cardiologists; and (3) identify additional medical and nonmedical factors affecting PCP echocardiogram ordering. An online survey with clinical scenarios derived from the AUC guidelines was distributed to PCPs and trainees in Arkansas, and pediatric cardiologists from Arkansas Children's Hospital and Cincinnati Children's Hospital Medical Center. Respondents were also asked to rate whether additional medical and nonmedical factors have "no," "mild," "moderate," or "major" impact on PCP echocardiogram ordering. Survey data were collected from 148 respondents. Awareness of the AUC was significantly lower in PCPs (21.4%) and trainees (14%) than in pediatric cardiologists (90.5%, p 0.001). For all rarely appropriate clinical scenarios, cardiologists had stronger agreement with the AUC document (90.9%) than did the PCP group (50.3%) and trainees (53.3%, p 0.001). The strongest additional factors affecting PCP echocardiogram ordering were parental anxiety, difficulty distinguishing innocent from pathologic murmurs, and legal implications of a missed diagnosis. In conclusion, PCPs and trainees are largely unaware of the existence of the pediatric echocardiogram AUC. Educational strategies to improve appropriate echocardiogram ordering should address not only increasing awareness of AUC, but also other factors affecting decision-making.

Patients with hypoplastic left heart syndrome (HLHS) can have associated genetic abnormalities. This study evaluated the incidence of genetic abnormalities among infants with HLHS and the short-term outcomes of this population during the first hospitalization. This is a retrospective analysis of the multi-center Pediatric Heath Information System database of infants with HLHS who underwent Stage I Norwood, Hybrid, or heart transplant during their first hospitalization from 2004 through 2013. We compared clinical data between infants with and without genetic abnormality, among the three most common chromosomal abnormalities, and between survivors and non-survivors. Multivariable analysis was completed to evaluate predictors of mortality among patients with genetic abnormalities. A total of 5721 infants with HLHS were identified; 282 (5%) had associated genetic abnormalities. The three most common chromosomal abnormalities were Turner (25%), DiGeorge (22%), and Downs (12.7%) syndromes. Over the study period, the number of patients with genetic abnormalities undergoing cardiac operations increased without any significant increases in mortality. Infants with genetic abnormalities compared to those without abnormalities had longer hospital length of stay and higher morbidity and mortality. Variables associated with mortality were lower gestational age, longer duration of vasopressor therapy, need for dialysis, and cardiopulmonary resuscitation; and complicated clinical course as suggested by necrotizing enterocolitis, septicemia. Presence of any genetic abnormality in infants with HLHS undergoing cardiac surgery is associated with increased mortality and morbidity. Timely genetic testing, appropriate family counseling, and thorough preoperative case selection are suggested for these patients for any operative intervention.

Objective To characterize supervision levels across residential settings at 1 year post-TBI and explore predictors of supervision in a Veteran and Service-member population. Setting Five VA Polytrauma Rehabilitation Centers. Participants A total of 302 individuals enrolled in the VA TBI Model Systems (TBIMS) research program. Design Prospective, longitudinal, multisite. Main measures Primary residence and supervision levels measured via scores on the Supervision Rating Scale. For predictive modeling, scores were dichotomized into 2 groups: those that were fully independent/living alone or required only some supervision during the day (independent group, n = 195) and those that required overnight supervision, full-time indirect supervision, and full-time direct supervision (dependent group, n = 107). Results Thirty-five percent were receiving supervision at 1 year post-TBI across residential settings and 28% were living in alternative settings. Multivariate modeling indicated that older age and longer posttraumatic amnesia (PTA) were predictive of having a need for supervision at 1 year postinjury. Conclusions Supervision needs are long-term features of moderate and severe TBI. Results of this study lend support to the shift toward conceptualizing TBI as a chronic disease.

OBJECTIVE To explore stability of relationships and predictors of change in relationship status 2 years following TBI/polytrauma. SETTING Five Department of Veterans Affairs Polytrauma Rehabilitation Centers (VA PRCs). PARTICIPANTS A total of 357 active duty service members and Veterans enrolled in the Veterans Affairs Polytrauma Rehabilitation Centers Traumatic Brain Injury Model Systems database with complete marital status information at 2 years postinjury. DESIGN Prospective, longitudinal, multisite. MAIN MEASURES Relationship status change was defined as change in marital status (single/never married; married; divorced/separated) at 2-year follow-up, compared with status at enrollment. RESULTS At the time of enrollment, 134 participants (38%) were single/never married; 151 (42%) were married, and 72 (20%) were divorced/separated. Of those married at enrollment, 78% remained married at year 2 while 22% underwent negative change. Multivariable analyses revealed that age and education at the time of injury and mental health utilization prior to injury were significant predictors of relationship change. Among those who were single/divorced/separated at the time of enrollment, 87% remained so at year 2 while 13% underwent positive change. Injury during deployment significantly predicted positive relationship change. CONCLUSIONS The unmalleable, preinjury characteristics identified may be used as potential triggers for education, prevention, surveillance, and couples therapy, if needed.

Background Body surface area (BSA)-indexed Z-scores are used to assess the ascending aorta (AAo) and diagnose aortic dilation (AoD) in children. BSA is directly related to body weight and corresponds to body mass index (BMI). We hypothesized extremes in BMI alter interpretation of aortic size in pediatric patients with AoD. Methods We reviewed all echocardiograms with a diagnosis of AoD performed at our institution from January 2013 through June 2013. Those with an age 20 years, history of aortic root surgery, or inadequate images were excluded. The aorta was measured by standard methods at the sinus of Valsalva, sinotubular junction, and proximal AAo. Using subject age, height, and gender, hypothetical weights for each subject were calculated to provide BMIs corresponding to the 5th, 50th, 85th, and 95th percentiles. The derived weights were then used to determine hypothetical BSA, and Z-scores were calculated for the subject's aortic diameters in each BMI group. Results A total of 153 patients met inclusion criteria. Mean age was 11.1±4.6 years (68% male). Mean height was 142.7±27.9 cm, mean weight 44.6±24.8 kg, and mean true BMI was the 62nd centile. Significant differences in all aortic dimension Z-scores were found among normal and underweight, overweight, and obese BMI groups (P

Background Limited literature has examined characteristics of infants with hypoplastic left heart syndrome (HLHS) who remain hospitalized during the interstage period. We described their epidemiologic characteristics, in-hospital outcomes, and identified risk factors that predict the need for superior cavopulmonary anastomosis (SCPA) during the same hospitalization. Methods This retrospective multicenter database analysis included infants with HLHS who underwent stage 1 palliation from 2004 through 2013. Results Among 5374 infants with HLHS, 314 (5.8%) underwent SCPA during the same hospitalization as stage 1 palliation. They had a higher incidence of baseline comorbidities, complications, and interventions than infants who were discharged. Despite an overall increase in need for SCPA in the same hospitalization across different eras, there was no significant statistical difference in mortality in the two groups in the same era. Septicemia, necrotizing enterocolitis, modified Blalock-Taussig shunt, cardiac catheterization, cardiopulmonary resuscitation, extracorporeal membrane oxygenation, gastrostomy tube, and antiarrhythmic agents were independently associated with increased odds of undergoing SCPA during the same hospitalization. Patients undergoing right ventricle to pulmonary artery shunt were less likely to remain hospitalized until stage 2 palliation. Nonsurvivors in the SCPA group had greater need for interventions and worse intensive care unit outcomes. Conclusions Infants with HLHS who remain hospitalized after stage 1 until their stage 2 palliation differ significantly from infants who were discharged. Several clinical characteristics, comorbidities, and need for interventions are associated with the likelihood for undergoing stage 2 palliation during the same hospitalization. Timely identification and intervention of adjustable causes of heart failure may improve outcomes.

// Yan Yang 1 , Wei Pan 2 , Xinyu Tang 1 , Shuqing Wu 3 and Xinchen Sun 1 1 Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 2 Department of Radiation Oncology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China 3 Department of Radiation Oncology, The Affiliated Danyang Hospital of Nantong University, Nantong, China Correspondence to: Shuqing Wu, email: // Xinchen Sun, email: // Keywords : breast cancer, anastrozole, tamoxifen, meta-analysis Received : February 06, 2017 Accepted : March 04, 2017 Published : March 22, 2017 Abstract Whether anastrozole has superior effects to tamoxifen for breast cancer remains controversial. Therefore, we conducted this meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of anastrozole versus tamoxifen as adjuvant therapy in breast cancer. A systematic literature search of PubMed, Web of Science, Embase, and Cochrane library were performed to evaluate the survival benefits and toxicity profiles of patients with breast cancer who were treated with anastrozole or tamoxifen. The main outcome measures included disease-free survival (DFS), recurrence-free survival (RFS), overall survival (OS), overall response rate (ORR), and adverse events. Hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a fixed-effects model or random-effects model. Nine RCTs with a total of 15,300 patients met the inclusion criteria and were included in this meta-analysis. Pooled estimates suggested that, anastrozole was associated with a significantly improvement in DFS (HR=0.72, 95%CI: 0.55-0.94; P =0.016), and ORR (RR=1.21, 95% CI: 1.05-1.39; P =0.009) than tamoxifen. But it did not prolong OS (HR=0.96, 95%CI: 0.77-1.21; P =0.751). Compared with tamoxifen, anastrozole induced a higher incidence of arthralgia (RR=1.55, 95%CI: 1.20-1.99; P =0.001) and bone pain (RR=1.31, 95%CI: 1.05-1.62; P =0.015), as well as a lower incidence of vaginal bleeding (RR=0.51, 95%CI: 0.28-0.93; P =0.029), vaginal discharge (RR=0.31, 95%CI: 0.12-0.82; P =0.017), and thromboembolic events (RR=0.39, 95%CI: 0.28-0.55; P

L-3,4-dihydroxyphenylalanine (L-DOPA) is currently the main drug used to treat Parkinson's disease (PD). However, long-term use of l -DOPA causes substantial side effects, and we hope to find a biological active ingredient that synergizes with a low-dose of l -DOPA to achieve the same therapeutic effect as that of a high-dose of l -DOPA. The natural product parthenolide (PTL) is the active ingredient in the medicinal plant feverfew (Tanacetum parthenium) and has antioxidant and anti-inflammatory properties. ACT001, a fumarate salt form of dimethylaminomicheliolide (DMAMCL), is a derivative of parthenolide and has comparable effects to those of PTL but exhibits higher stability in the plasma and is available at a lower cost. In our study, we used ACT001 in combination with l -DOPA to treat 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease in mice. Specifically, ACT001 significantly reduced motor dysfunction and dopaminergic neurodegeneration in MPTP-treated mice. Furthermore, ACT001 abolished MPTP-induced α-synuclein overexpression, astrocyte activation and interleukin-1β (IL-1β) production in the substantia nigra and striatum of the mouse brain. In addition, ACT001 increased the levels of the anti-apoptotic signalling molecule Bcl-2 and the pAkt/Akt ratio and reduced the levels of the pro-apoptotic signalling molecule Bax and the activation of Caspase3 in the substantia nigra and striatum. We found that the effects of the co-administration of ACT001 and l -DOPA (5 mg/kg) were equivalent to those of the administration of 8 mg/kg l -DOPA in MPTP-induced Parkinson's disease in mice. Then, this evidence suggests that l -DOPA + ACT001 may be used for the treatment of PD.

Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease, making up 10% of all congenital heart defects. Annual follow-up echocardiograms are recommended in patients with repaired ToF, but evidence-based guidelines do not exist. We hypothesized that most echocardiograms performed in asymptomatic patients with repaired ToF and no physical exam change do not result in an actionable change (AC) in management. We retrospectively reviewed records of all patients with ToF and prior complete repair at our institution between January 2000 and September 2015. Changes in echocardiograms resulting in hospital admission, medication addition/change, cardiac catheterization, or surgical procedure were identified via chart review. These changes were referred to as an AC. A total of 1135 echocardiograms were reviewed from 233 patients (160 with initial complete repair, 70 with prior shunt, and 3 with other initial surgery). The median number of echocardiograms per patient was 5. Of the 1135 echocardiograms, 15 (1.3%) were associated with AC. Of the 15 patients with AC echocardiograms, 9 underwent a shunt prior to complete repair (9/70, 12.9%) and 6 had undergone an initial complete repair (6/160, 3.8%). The median age at AC was 6.3 years (IQR 4.4, 6.8) in the shunt group and 0.90 years (IQR 0.87, 1.1) in the initial complete repair group. In asymptomatic patients with repaired ToF and no physical exam change, echocardiograms rarely lead to a change in clinical management. In conclusion, the likelihood and timing of AC echocardiograms and reinterventions vary based on the type of initial surgery.

L-DOPA (L-3,4-dihydroxyphenylalanine) relieves symptoms of Parkinson disease (PD), but long-term use can cause serious side effects. Resveratrol (3,5,4′-trihydroxy-trans-stilbene, RV), a polyphenolic compound derived from grapes and red wine that has antioxidant activity, has been shown to have neuroprotective effects. RV was investigated to enhance the therapeutic effect of L-DOPA in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson disease. Mice received a saline or RV injection (10 mg/kg/day), then 2 h later, saline or MPTP (15 mg/kg/day) was administered for 7 consecutive days. Saline or L-DOPA (5 or 8 mg/kg/day) was injected post-administration of MPTP for the last 2 consecutive days. Our results indicated that RV alleviated MPTP-induced loss of dopaminergic neurons and attenuated astroglial activation in the nigrostriatal pathway. In parallel, RV reduced the expression of α-synuclein in the striatum. In addition, RV also increased levels of the anti-apoptotic signalling molecule Bcl-2, reduced levels of the pro-apoptotic signalling molecule Bax, and reduced activation of caspase-3 in the striatum. Specifically, RV significantly reduced motor dysfunction in MPTP-treated mice. Furthermore, the RV-treated group showed less IL-1β and an enhanced pAkt/Akt ratio, which promoted dopamine neuron survival in the striatum. We found that the effects of co-administration of RV with L-DOPA (5 mg/kg) were equivalent to those of administration of 8 mg/kg L-DOPA in MPTP-induced PD mice. Therefore, with fewer side effects, L-DOPA can be effectively used in the treatment of PD over a long period of time.

Chronic metabolic diseases are on the rise worldwide and their etiology is multifactorial. Among them, inflammatory components like Tumor Necrosis Factor (TNF), contribute to whole-body metabolic impairment. Caloric Restriction (CR) combats metabolic diseases, but how it reduces inflammation remains understudied. We aimed to evaluate the impact of chronic CR on muscle inflammation, in particular TNF. In our study, 4-week old male Sprague-Dawley rats were fed a high-fat diet (HF, 45% Kcal of fat from lard) ad libitum for 3 months. After estimation of their energy requirement (1 month), they were then divided into three groups: HF ad libitum (OL), weight maintenance with AIN93M (9.5% Kcal from fat; ML, 100% of energy requirement), and caloric restriction (CR, AIN93M with 75% of energy requirement). This dietary intervention continued for six months. At this point, rats were sacrificed and gastrocnemius muscle was collected. CR induced a profound shift in fat and lean mass, and decreased growth factor IGF-1. Muscle qPCR analysis showed a marked decrease in inflammation and TNF (premRNA, mRNA, and protein) by CR, accompanied by Tnf promoter DNA hypermethylation. CR increased expression of histone deacetylase Sirt6 and decreased methyltransferase Suv39h1, together with decreased Tnf promoter and coding region binding of NF- κB and C/EBP-β. Following miRNA database mining, qPCR analysis revealed that CR downregulated the proinflammatory miR-19b and increased the anti-inflammatory miR-181a and its known targets. Chronic CR is able to regulate muscle-specific inflammation by targeting the NF-κB pathway as well as transcriptional and post-transcriptional regulation of Tnf gene.

Previous research on risk factors for obstructive heart defects (OHDs) focused on maternal and infant genetic variants, prenatal environmental exposures, and their potential interaction effects. Less is known about the role of paternal genetic variants or environmental exposures and risk of OHDs. We examined parent-of-origin effects in transmission of alleles in the folate, homocysteine, or transsulfuration pathway genes on OHD occurrence in offspring. We used data on 569 families of liveborn infants with OHDs born between October 1997 and August 2008 from the National Birth Defects Prevention Study to conduct a family-based case-only study. Maternal, paternal, and infant DNA were genotyped using an Illumina Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR), 95% confidence interval (CI), and likelihood ratio tests from log-linear models were used to estimate the parent-of-origin effect of 877 SNPs in 60 candidate genes in the folate, homocysteine, and transsulfuration pathways on the risk of OHDs. Bonferroni correction was applied for multiple testing. We identified 3 SNPs in the transsulfuration pathway and 1 SNP in the folate pathway that were statistically significant after Bonferroni correction. Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively, compared to infants who inherited maternally-derived copies of the same alleles. We observed statistically significant decreased risk of OHDs among infants who inherited paternal gene variants involved in folate and transsulfuration pathways., Author summary Obstructive heart defects are birth defects that cause obstruction to the blood flow of the developing heart. Common OHDs include coarctation of the aorta, aortic stenosis and pulmonary stenosis. While there is a fair amount of literature indicating an association between maternal genetic variants and OHDs, less is known about the role of paternal genetic variants in the etiology of OHDs. We used a genotype clustering algorithm, SNPMClust, that was developed in-house at the Arkansas Center for Birth Defects Research and Prevention to study the role of paternal genetic variants in the folate, homocysteine and transsulfuration pathways. Maternal, paternal, and infant DNA specimens were collected from participants of the National Birth Defects Prevention Study, a large population-based case-control study in the United States, and were genotyped using an Illumina Golden Gate custom single nucleotide polymorphism (SNP) panel. We identified 4 SNPs in the folate and transsulfuration pathways, rs6812588, rs1762430, rs9296695, and rs4712023, that were associated with a statistically significant decreased risk of OHDs for infants who inherited a paternally-derived copy of the variant allele compared to infants who inherited a maternal copy of the variant allele. In conclusion, we observed a significantly decreased risk and less epigenetic influence of paternal genetic variants on OHDs compared to maternally-derived variants.

Objective Multiple reports have shown echocardiograms for certain indications are neither cost-effective nor of high diagnostic yield. Given the ease with which tests can be obtained at a tertiary academic children's hospital, our aims were to: (1) determine the diagnostic yield of inpatient studies by in-hospital location; (2) evaluate inpatient echocardiograms to determine indications and level of appropriateness; and (3) evaluate the frequency of cardiology involvement prior to those echocardiograms. Design All initial inpatient echocardiograms interpreted at our institution from February 2009 to December 2014 were reviewed retrospectively. Patient location was grouped as pediatric intensive care (PICU), emergency department (ED), and general floor. Results There were 727 first-time inpatient echocardiograms that met inclusion criteria. Pathology was identified in 25% of the study echocardiograms, with 11% of all studies demonstrating pathology that could alter patient management (moderate or severe pathology). The studies performed in the PICU and ED had more severe pathology compared with those from the general floor (P

Child abuse is a major public health concern that can explain a proportion of fractures in children. Osteogenesis imperfecta (OI) is the most common inherited syndrome that predisposes to skeletal fractures. We conducted a retrospective analysis of data from clinical, laboratory, and radiographic information from children evaluated for child abuse in which molecular testing for COL1A1 and COL1A2 genes was conducted. A total of 43 patients underwent molecular testing for OI. Pathogenic variants predicted to result in a mild form of OI were found in two patients (5%), both clinically suspected to have this diagnosis. None of the cases in whom OI molecular testing was ordered when maltreatment concerns were thought to be more likely (0/35) were identified to have pathogenic variants. After reviewing each individual case, the final diagnosis was child abuse for 34 cases (77%), and additional radiographic and laboratory studies did not identify any with inherited metabolic predisposition to fracture or rickets. We conclude that routine testing for OI in the setting of child abuse when no other suggestive clinical findings are present has a low yield. A careful review of the medical history and a detailed clinical evaluation help identify those at risk for genetic alterations. © 2016 Wiley Periodicals, Inc.

Background We describe the clinical characteristics and epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in children with cystic fibrosis (CF) from the U.S. CF center with the highest MRSA prevalence. Methods Medical records of children with CF were retrospectively reviewed from 1997-2009. MRSA clinical isolates from 2007-2009 were analyzed by polymerase chain reaction and pulsed field gel electrophoresis. Results The prevalence of MRSA was 1% in 1997 and 49% in 2009. Fifty-five children (26%) had persistent MRSA infection. Sixty-eight percent of MRSA isolates were hospital-associated (HA) MRSA, of which 52% were pulsed-field type USA 100. Ninety-three percent of HA MRSA isolates were clindamycin resistant. Twelve children acquired MRSA before 1 year of age, 83% of whom were hospitalized prior to acquisition of MRSA. Ten of 11 sibling pairs carried indistinguishable MRSA strains. Children with persistent MRSA were hospitalized more often ( P = .01), required inhaled medications more frequently ( P = .01), and had higher rates of Pseudomonas aeruginosa coinfection ( P Conclusion MRSA prevalence in children with CF is increasing, and most children are infected with HA MRSA. Exposure to health care facilities and gastrointestinal surgeries may facilitate early acquisition of MRSA. Siblings carry indistinguishable MRSA strains, indicating household transmission of MRSA. Children with persistent MRSA had worse pulmonary morbidity. Coinfection with MRSA and P aeruginosa is likely associated with further increased pulmonary morbidity.

Parkinson's disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and dementia. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can lead to some Parkinson's-like symptoms by destroying dopaminergic neurons in the substantia nigra of the brain. It has been thus used to establish PD models in various animal studies. Here, mice receive MPTP injections (20 mg/kg/day) for seven days and the behavioral tests are performed on the eighth day. This model is adapted efficiently in the study of PD. The behavioral tests here include the cylinder test and the open field test. The cylinder experiment is used to detect the animals' ability to lift their front paws when put into a different environment. As the PD model mice show arching-the mouse arches its back-the number of paw liftings decrease. This test is easy to execute. The open field test is used to detect the amount of time the mice spend on running, walking, and remaining immobile. We analyze animals' movements in open field using software and obtain data. Lastly, we use L-DOPA, one of the most commonly used PD drugs, as one example to show how to apply this model to the study of PD drugs. Our results indicate that MPTP neurotoxicity induces motor deficit which can be mitigated by L-DOPA.

Data investigating the impact of household income and other factors on SV patient status-post-Fontan palliation after heart transplantation are lacking. We aim to evaluate factors affecting outcomes after OHT in this population. The PHIS database was interrogated for either SV or myocarditis/primary CM who were 4 years or older who underwent a single OHT. There were 1599 patients with a median age of 13.2 years (IQR: 9.3-16.1). Total hospital costs were significantly higher in the SV group ($408 000 vs $294 000, P

Few studies have assessed the long-term functional outcomes of patients with a disorder of consciousness due to traumatic brain injury (TBI). This study examined functional status during the first 10 years after TBI among a cohort with disorders of consciousness (i.e., coma, vegetative state, minimally conscious state). The study sample included 110 individuals with TBI who were unable to follow commands prior to inpatient rehabilitation and for whom follow-up data were available at 1, 2, 5, and 10 years post-injury. The sample was subdivided into those who demonstrated command-following early (before 28 days post-injury) versus late (≥ 28 days post-injury or never). Functional Independence Measure (FIM) at 1, 2, 5, and 10 years following TBI was used to measure functional outcomes. Measureable functional recovery occurred throughout the 10-year period, with more than two thirds of the sample achieving independence in mobility and self-care, and about one quarter achieving independent cognitive function by 10 years. Following commands prior to 28 days was associated with greater functional independence at all outcome time-points. Multi-trajectory modeling of recovery of three FIM subscales (self-care, mobility, cognition) revealed four distinct prognostic groups with different temporal patterns of change on these subscales. More than half the sample achieved near-maximal recovery by 1 year post-injury, while the later command-following subgroups recovered over longer periods of time. Significant late functional decline was not observed in this cohort. Among a cohort of patients unable to follow commands at the time of inpatient rehabilitation, a substantial proportion achieved functional independence in self-care, mobility, and cognition. The proportion of participants achieving functional independence increased between 5 and 10 years post-injury. These findings suggest that individuals with disorders of consciousness may benefit from ongoing functional monitoring and updated care plans for at least the first decade after TBI.

Obstructive heart defects (OHDs) are a major health concern worldwide. The platelet-derived growth factor (PDGF) genes are known to have regulatory functions that are essential for proper heart development. In a zebrafish model, Pdgfra was further demonstrated to interact with ethanol during craniofacial development. In this article, we investigated interactions between variants in PDGF genes and periconceptional alcohol exposure on the risk of OHDs by applying log-linear models to 806 OHD case and 995 control families enrolled in the National Birth Defects Prevention Study. The interactions between four variants in PDGFA and maternal binge drinking reached a nominal significance level. The maternal T allele of rs869978 was estimated to increase OHD risk among women who binge drink, while infant genotypes of rs2291591, rs2228230, rs1547904, and rs869978 may reduce the risk. Although none of these associations remain statistically significant after multiple testing adjustment and the estimated maternal effect may be influenced by unknown confounding factors, such as maternal smoking, these findings are consistent with previous animal studies supporting potential interactions between the PDGFRA gene and maternal alcohol exposure. Replication studies with larger sample sizes are needed to further elucidate this potential interplay and its influence on OHD risks.

To describe change in body mass index (BMI) and weight classification 1-year post- traumatic brain injury (TBI) among Veterans and service members.Prospective observational cohort study.VA Polytrauma Rehabilitation Centers.Veterans and service members (N = 84) enrolled in VA Traumatic Brain Injury Model Systems (VA TBIMS) study with BMI scores at enrollment and 1-year post-injury.N/A.BMI scores from height and weight and weight classifications (underweight, normal weight, overweight, obese classes 1-3) defined by WHO.Twenty per cent were obese at time of injury and 24% were obese at 1-year post-injury. Cross-tab analyses revealed 7% of normal weight and 24% overweight participants at time of injury as obese Class 1 one-year post-injury. Univariate models found BMI and tobacco smoking at time of injury were significant predictors of higher BMI scores 1-year post-TBI. Multivariable models found BMI at time of injury and motor functioning, were significant predictors. Preinjury BMI, tobacco smoking and PTSD symptom severity predicted change in weight category.While obesity among service members and Veterans post-TBI is below national averages, trends in weight gain between time of injury and 1-year follow-up were observed. Implications for health promotion and chronic disease management efforts with regards to rehabilitation for injured military are discussed. List of Abbreviations: BMI, Body mass index; BRFSS, Behavioural Risk Factor Surveillance; GCS, Glasgow Coma Scale; FIM, Functional Independence Measure; NIDILRR, National Institute on Independent Living and Rehabilitation Research; PCL-C, PTSD checklist-civilian; PSTD, Post-traumatic stress disorder; VA, Veterans Affairs; VA PRC, Veterans Affairs Polytrauma Rehabilitation; VA TBIMS, Veterans Affairs TBI Model Systems.

Pulmonary artery (PA) stenosis is the most common late sequela following arterial switch for d-transposition of the great arteries. The purpose of this study was to assess the effectiveness of transthoracic echocardiography in evaluating the pulmonary arteries following repair. This was a retrospective, cross-sectional analysis of all echocardiograms performed on patients following arterial switch operation. A numerical scoring system was devised and used to quantify PA visualization based on 2D images, color mapping, and spectral Doppler. The study cohort included 150 patients. The ability to visualize at least one PA was poorer in patients who were older [> 10 years (47%) vs ≤ 10 years (89%) (p 1.25 m2 (40%) vs ≤ 1.25 m2 (90%) (p

SummaryObjective The results from a recent national survey about catastrophic complications following tracheostomy revealed that the majority of events involved a loss of airway. Most of the events due to airway loss involved potentially correctable deficits in caregiver education. Training in a simulated environment allows skill acquisition without compromising patient safety. We assessed the knowledge and confidence level of pediatric health care providers at a large tertiary care children's hospital in routine and emergency tracheostomy care and evaluated the efficacy of a comprehensive simulation-based tracheostomy educational program. Methods The prospective observational study was comprised of 33 subjects including pediatric residents, internal medicine–pediatric residents, pediatric hospitalist faculty physicians, and advanced practice registered nurses who are involved in the care of patients with tracheostomies within a tertiary-care children's hospital. The subjects completed self-assessment questionnaires and objective multiple-choice tests before and after attending a comprehensive educational course that employed patient simulation. The outcome measurements included pre- and post-course questionnaires, pre- and post-course test scores, and observational data from the simulation sessions. Results Before the education and simulation, the subjects’ comfort and confidence levels on a five-point Likert scale in performing routine tracheostomy tube care, routine tracheostomy tube change, and an emergency tracheostomy tube change were as follows (median (Q1, Q3)): 1 (1, 2), 1 (1, 2), and 1 (1, 2), respectively (n = 28). The levels of comfort and confidence after completing the course improved significantly to 4 (4, 5), 4 (4, 5), 4 (4, 5), respectively (P

Congenital heart defects (CHDs) develop through a complex interplay between genetic variants, epigenetic modifications, and maternal environmental exposures. Genetic studies of CHDs have commonly tested single genetic variants for association with CHDs. Less attention has been given to complex gene-by-gene and gene-by-environment interactions. In this study, we applied a recently developed likelihood-ratio Mann-Whitney (LRMW) method to detect joint actions among maternal variants, fetal variants, and maternal environmental exposures, allowing for high-order statistical interactions. All subjects are participants from the National Birth Defect Prevention Study, including 623 mother-offspring pairs with CHD-affected pregnancies and 875 mother-offspring pairs with unaffected pregnancies. Each individual has 872 single nucleotide polymorphisms encoding for critical enzymes in the homocysteine, folate, and trans-sulfuration pathways. By using the LRMW method, three variants (fetal rs625879, maternal rs2169650, and maternal rs8177441) were identified with a joint association to CHD risk (nominal P-value = 1.13e-07). These three variants are located within genes BHMT2, GSTP1, and GPX3, respectively. Further examination indicated that maternal SNP rs2169650 may interact with both fetal SNP rs625879 and maternal SNP rs8177441. Our findings suggest that the risk of CHD may be influenced by both the intragenerational interaction within the maternal genome and the intergenerational interaction between maternal and fetal genomes.

Aim To evaluate the association of house staff training with mortality in children with critical illness. Methods Patients

Transcatheter pulmonary valve replacement (TC-PVR) is an alternative to surgical PVR (S-PVR) in repaired Tetralogy of Fallot (TOF). The purpose of this study is to compare in-hospital outcomes, hospital costs, and projected 5-year total costs of S-PVR to TC-PVR in patients with repaired TOF. We performed a multicenter, retrospective cohort study of children and adults with TOF ≥ 8 years of age who underwent PVR from January 1, 2010 to December 31, 2016 at 46 centers contributing to the Pediatric Health Information Systems database. Baseline characteristics, in-hospital outcomes, and costs were compared between the two groups. Projected 5-year costs were calculated by combining cost data with published reintervention rates. A total of 194 TC-PVR and 1,072 S-PVR were performed. The baseline characteristics of the TC-PVR and S-PVR groups were not significantly different with the exception of greater age in the TC-PVR group (median age of 17 years vs 15 years, p value

Paclitaxel‑based chemotherapy is a promising approach for prostate cancer treatment. However, single‑drug chemotherapy is associated with an increased risk of drug resistance. Therefore, novel combination chemotherapy regimens are a popular topic of research. Zinc participates in the regulation of apoptosis, for example in the form of Zn2+ and via zinc‑dependent enzymes. Zinc can either induce or suppress apoptosis, and its effect depends primarily on its concentration. Previous research has demonstrated that physiological concentrations of zinc can directly induce apoptosis of PC‑3 prostate cancer cells via the mitochondrial pathway. In prostate cancer tissues, zinc concentrations have been demonstrated to be reduced compared with non-cancerous tissues. Furthermore, the concentration of zinc has been demonstrated to decrease further with cancer progression. In the present study, it was investigated whether exposure of PC‑3 cells to zinc improved their sensitivity to the chemotherapeutic agent, paclitaxel. MTT assays, cell clone formation assays, Hoechst staining and flow cytometry revealed that zinc enhanced PC‑3‑cell chemosensitivity to paclitaxel. Western blotting and reverse transcription‑polymerase chain reaction were used to determine that the mitochondria‑mediated apoptosis signaling pathway is involved with zinc/paclitaxel‑induced cell death. The present study provides a foundation for the development of novel tumor combination therapy.

Objective To identify preinjury variables related to mental health treatment utilization at 2 years post-traumatic brain injury (TBI). Setting Veterans Affairs (VA) TBI Model Systems includes 5 VA Polytrauma Rehabilitation Centers. Participants Veterans and service members enrolled in TBI Model Systems who completed the year 2 follow-up assessment and provided mental health information. Sample was largely male (97%) and White (72%), with median age of 30 years. Design Participants with elevated mental health symptoms were identified by measures of depression, anxiety, and posttraumatic distress; suicide attempt in the past year; or problematic substance use in the past year. Forty-seven percent of participants had elevated mental health symptoms at 2 years postinjury. Among those with elevated symptoms, comparisons were made between those who sought mental health treatment in past year and those who did not. Main measures Demographic, historic, environmental, psychological/mental health, and injury/rehabilitation variables. Results Within the sample, 23% denied utilizing mental health services. Nonutilizers were more likely to deny a preinjury mental health treatment history, to report problematic substance use at year 2, and to report lower levels of internalizing symptoms than the treatment utilizers. Conclusion Veterans and service members with elevated mental health symptoms may require tailored tactics to promote treatment utilization post-TBI.

Objectives To present initial descriptive findings from the Veterans Affairs (VA) Polytrauma Rehabilitation Centers (PRC) Traumatic Brain Injury (TBI) Model Systems (MS) National Database. Design Prospective cohort study. Setting VA PRC TBIMS National Database. Participants 712 service members and veterans with TBI who consented to participate between January 2010 and June 2015. Interventions Not applicable. Main Outcome Measures Demographics, preinjury characteristics, injury characteristics, rehabilitation course, functional outcomes, and discharge disposition by TBI severity level. Results The study cohort was predominantly male with moderate to severe TBI secondary to vehicular accident or blast injury. Sixty-five percent were active duty service members; one-third had been injured during deployment. One-third reported mental health treatment and/or alcohol use problems in the year predating the index TBI. The median number of days between injury and PRC admission was 42.5. Nearly 25% reported clinical levels of posttraumatic stress disorder; 75% reported mild to moderate neurobehavioral symptomatology. The median length of stay in the PRC was 36 days; those with severe TBI had the longest lengths of stay. Functional independence ratings improved from admission to discharge across all TBI severity levels. A majority were discharged to urban areas to reside with spouses or other residents in private residences or adult homes, with some variability by injury severity. Conclusions The VA PRC TBIMS national database is a rich source of information on a unique group of individuals with TBI and promises to complement existing knowledge on TBI in the civilian population.

Little is known about the causes and risks of non-postoperative pericardial effusion (PCE) in pediatric patients. We sought to assess the diagnoses most frequently associated with admissions for PCE, and to determine if certain conditions were associated with higher in-hospital mortality and rates of readmission. Nationally distributed data from 44 pediatric hospitals in the 2004–2015 Pediatric Health Information System database were used to identify patients with hospital admissions for International Classification of Disease, Ninth Revision (ICD-9) codes for PCE and/or cardiac tamponade. Children with congenital heart disease were excluded. ICD-9 codes for conditions associated with PCE were grouped into eight categories: neoplastic, renal, autoimmune/inflammatory, pneumonia, viral, bacterial, hypothyroidism, and idiopathic. Multivariable models were used to evaluate odds of in-hospital mortality and readmission within 30 and 90 days. There were 9902 patients who met inclusion criteria. Total in-hospital mortality was 8.2% (n = 813); of those without a neoplastic diagnosis, mortality was 6.5% (n = 493/7543). Idiopathic PCE accounted for the most admissions (36%), followed by neoplasms (24%), pneumonia (20%), and autoimmune/inflammatory disease (19%). In multivariable models, odds of death were highest for neoplasms (adjusted odds ratio 3.83, p

Research among a wide range of cohorts (e.g. civilian, military) has increasingly highlighted traumatic brain injury (TBI) as a risk factor for suicidal thoughts and behaviors, including death by suicide. With this recognition, subsequent changes in clinical practice, such as TBI screenings among individuals seeking mental health services, as well as suicide risk assessment among individuals seeking rehabilitation services are essential. Information provided below is aimed at highlighting key and emerging findings regarding suicide and TBI, with the goal of encouraging providers and researchers to explore changing and expanding evidence-based clinical practices to match the needs of those living with a history of TBI.

Purpose: A kaolin-impregnated hemostatic sponge (QuikClot) is reported to reduce intraoperative blood loss in trauma and noncardiac surgery. The purpose of this study was to assess if this sponge was effective for hemostasis during Norwood operation. Description: We conducted a retrospective review of patients undergoing Norwood operation in infancy between 2011 and 2016 at our institution. Evaluation: Of 31 identified Norwood operations, a kaolin-impregnated sponge was used intraoperatively in 15 (48%) patients. The preoperative profiles and cardiopulmonary bypass status were similar between the operations with or without kaolin-impregnated sponge. The comparison on each operative outcome between operations with or without kaolin-impregnated sponge showed that the intraoperative platelets, cryoprecipitate, and factor VII dosage were significantly less in the operations with kaolin-impregnated sponge (55 mL, 10 mL, 0 µg/kg vs 72 mL, 15 mL, 45 µg/kg; P = .03, .021, .019), as well as the incidence of perioperative bleeding complications (second cardiopulmonary bypass for hemostasis or postoperative mediastinal exploration, 0% vs 31%, P = .043). A logistic regression model showed that the nonuse of kaolin-impregnated sponge and longer aortic cross clamp time were associated with perioperative bleeding complication in univariable model ( P = .02 and .005). Conclusions: Use of kaolin-impregnated hemostatic sponge was associated with reduced blood product use and perioperative bleeding complications in Norwood operation at a single institution.

Objective Within the same time frame, compare the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) and VA Traumatic Brain Injury Model System (TBIMS) data sets to inform future research and generalizability of findings across cohorts. Setting Inpatient comprehensive interdisciplinary rehabilitation facilities. Participants Civilians, Veterans, and active duty service members in the VA (n = 550) and NIDILRR civilian settings (n = 5270) who were enrolled in TBIMS between August 2009 and July 2015. Design Prospective, longitudinal, multisite study. Main measures Demographics, Injury Characteristics, Functional Independence Measures, Disability Rating Scale. Results VA and NIDILRR TBIMS participants differed on 76% of comparisons (18 Important, 8 Minor), with unique differences shown across traumatic brain injury etiology subgroups. The VA cohort was more educated, more likely to be employed at the time of injury, utilized mental health services premorbidly, and experienced greater traumatic brain injury severity. As expected, acute and rehabilitation lengths of stay were longer in the VA with no differences in death rate found between cohorts. Conclusions Substantial baseline differences between the NIDILRR and VA TBIMS participants warrant caution when comparing rehabilitation outcomes. A substantive number of NIDILRR enrollees had a history of military service (>13%) warranting further focused study. The TBIMS participant data collected across cohorts can be used to help evidence-informed policy for the civilian and military-related healthcare systems.

OBJECTIVE To identify predictors of satisfaction with life in Veterans 1 year after traumatic brain injury (TBI). SETTING The VA TBI Model Systems (TBIMS) project includes 5 Veterans Affairs (VA) Polytrauma Rehabilitation Centers. PARTICIPANTS Veterans enrolled in the VA TBIMS study who completed the Satisfaction With Life Scale at year 1 follow-up. The sample is largely male (96%) and Caucasian (72%), with a median age of 27 years upon enrollment. DESIGN Prospective observational cohort study measuring including demographics (eg, education), preinjury variables (eg, mental health history and employment), and military variables (eg, injury during deployment and injury during active duty status). MAIN OUTCOME MEASURE Satisfaction With Life Scale. RESULTS Multivariate regression analyses revealed that age, marital status, preinjury employment status, preinjury mental health history, and active duty status at the time of injury were significant predictors of life satisfaction at year 1 follow-up. CONCLUSIONS Results of this study suggest that satisfaction with life in Veterans with TBI is mediated by several factors that might inform rehabilitation interventions and discharge recommendations. Preinjury variables and active duty status (a unique aspect of the Veteran population) influence life satisfaction at 1 year postinjury. Limitations and future clinical implications will be discussed.

The edible mushroom Lentinus edodes has been shown to offer medicinal effects including antifungal, antibacterial, antiviral, antioxidant, as well as anticancer activities. Assessment of bioactivit...

Objective To determine the incidence and causes of rehospitalization following military or Veteran traumatic brain injury (TBI). Setting Department of Veterans Affairs (VA) Veterans Health Administration Polytrauma Rehabilitation Centers (VHA PRCs). Participants Consecutive sample of VHA TBI Model System participants (N = 401). Design Prospective observational cohort study. Main measures Number and type of rehospitalizations in first year post-TBI. Results Forty-one percent of 401 participants were rehospitalized. Rehospitalization status was associated with greater injury severity and receipt of TBI while active duty. Of those rehospitalized, 30% had 2 or more readmissions. Participants experiencing multiple rehospitalizations (2+) were more likely to have sustained their TBI during deployment than those with none or single rehospitalization. This group also sustained more severe injuries and spent more time in VA PRC inpatient rehabilitation. Common reasons for rehospitalization included inpatient rehabilitation (33%), unspecified (26%), orthopedic (10%), seizures (8%), infection (8%), and psychiatric (7%). Conclusion This is the first study examining military and Veteran rehospitalization following TBI requiring inpatient rehabilitation at a VA PRC. Findings indicate frequent rehospitalizations in the first year postinjury, suggesting the need for preventive models of health maintenance following inpatient rehabilitation discharge. Greater surveillance of those with deployment-related TBI or active duty at the time of injury and greater TBI severity may be warranted.

This study demonstrated that a homogeneous polysaccharide (HPS) extracted from Hawthorn exerted anti-cancer effects on colon cancer cells. Human colon cancer cell line HCT116 were treated with 125–1000 µg/mL HPS for 12 h and subsequent analysis was performed on proliferation and signaling pathways. HPS significantly inhibited proliferation of HCT116 cells when analyzed using WST-1 assay and immunofluorescence staining of Ki-67. Flow cytometric studies revealed that HPS could arrest the cell cycle in the S and G2/M phases and increase the rate of apoptosis. HPS downregulated the expression of Cyclin A1/D1/E1 and CDK-1/2. HPS induced apoptosis on HCT116 cells through upregulation of caspase3, 7, 8, 9 and Fas, FADD, TNF-R1, TRADD, upregulation of caspase3 protein was also observed. HPS has an anti-cancer potential in the treatment of human colon cancer which makes it a potential candidate in functional foods for cancer patients.