Background Injuries are the leading cause of death in the United States for children between the ages of 1 and 19 years. Weekend hospital admission has been associated with poor outcomes and higher mortality rates for a variety of diseases. We examined the impact of weekend versus weekday admission on in-hospital morbidity and case-fatality rates for pediatric trauma patients. Methods We performed a cross-sectional analysis on the 2016 Kids’ Inpatient Database. The study population included pediatric trauma patients under the age of 19 years which were stratified by weekend vs weekday admission. Weightings were used to produce national estimates. Multiple logistic regression analyses were performed to assess the odds of in-hospital complications and death after adjusting for a variety of potentially confounding demographic and clinical factors. Results Patients admitted on a weekend were older, more frequently male, White, and privately insured. Weekend admissions had a higher Injury Severity Score (6.7 vs 5.4, p<0.001), as well as higher rate of intensive care unit (ICU) admission (8.5% vs 7.1%, p<0.001) and in-hospital case-fatality rate (1.3% vs 1.1%, p=0.003), but lower rate of in-hospital complications (6.1% vs 6.8%, p<0.001). Unadjusted logistic regression demonstrated that weekend admission was associated with higher odds of in-hospital death as compared to weekday admission (odds ratio 1.20, 95% confidence interval [CI] 1.07 – 1.35), but in the multivariable adjusted model this was no longer statistically significant (adjusted odds ratio [aOR] 1.06, 95% CI 0.94 – 1.20). Weekend admission was associated with lower odds of in-hospital complications (aOR 0.90, 95% CI 0.86 - 0.95), but higher odds of ICU admission (aOR 1.12, 95% CI 1.06 – 1.18). Conclusions Weekend admission in pediatric trauma is associated with higher odds of ICU admission. There does not appear to be an association between weekend admission and odds of in-hospital death, however it may be associated with lower odds of in-hospital complications.

Background: Bernard Soulier Syndrome (BSS) is a rare, autosomal recessive inheritance disorder of platelet function. Estimated to affect one per one million, there are currently only 200 cases reported worldwide presenting more commonly in families with parental consanguinity. This syndrome occurs when there is a genetic defect in the subunits (GPIb-alpha, GPIB-beta, and GP9) that form the GPIb-IX-V complex. The result is inadequate binding to von Willebrand factor. The clotting cascade is, therefore, unable to begin, causing symptoms of excessive and prolonged bleeding. Objectives: We report a case with multiple episodes of exaggerated bleeding and easy bruising. Methods: We analyzed complete blood count, coagulation studies, platelet aggregation assays, platelet glycoprotein expression by flow cytometry, as well as screened both patient and parents for relevant genes responsible for BSS. Results: 14-month-old Caucasian male born at 38w3d gestational age, non-consanguineous parents with multiple episodes of exaggerated bleeding and easy bruising from minor injuries. His symptoms started early in life with excessive bleeding after circumcision. No history of intramuscular, joint, or intracranial bleeding. Complete blood counts showed macrothrombocytopenia (98 X109 /L MPV 12.3 fl) no leukocyte inclusion bodies on peripheral smear. Coagulation tests (prothrombin time, activated partial thromboplastin time, vWF antigen, and vW-Ristocetin cofactor activity, platelet function assay) were normal. Platelet glycoprotein expression by flow cytometry revealed significantly reduced binding of monoclonal antibodies to platelet GPIb and normal GPIIb/IIIa. Comprehensive platelet disorder panel revealed two clinically significant variants missense mutations in the GP9 gene (P.Cys135 Tyr and P.Asn61Ser) These variants were on opposite alleles and results were consistent with the diagnosis of Bernard Soulier syndrome (BSS). The mother reported heavy menstrual cycles, the father had no significant bleeding symptoms, and both parents had normal platelet counts. Target genetic testing identified these two distinct missense mutations from both Mother and Father of the child. Conclusion: The two rare variants occurring on the gene for GPIX (GP9) increase the number of known genetic defects associated with the manifestation of Bernard Soulier Syndrome.

Propranolol, a first-generation nonselective β-adrenoceptor blocking agent, is commonly used to treat pediatric arrhythmias. Atenolol, relatively long-acting, cardioselective β-adrenoceptor blocking agent, has been successfully used in adults with supraventricular tachycardia (SVT). There is only one report on the use of atenolol in children with SVT, and our report is on the first long-term prospective study to evaluate the use of atenolol in children. A group of 22 children <18 years of age with clinical SVT were enrolled in the study. The tachycardia was documented on electrocardiograms in each case and was confirmed by electrophysiologic studies in some. Once- a-day oral atenolol was started as a monotherapy. Of the 22 children with various types of SVT, 13 (59%) were well controlled on long-term oral atenolol therapy. The effective dose of atenolol ranged between 0.3 and 1.3 mg/kg/day (median effective dose 0.7 mg/kg/day). Five children had some adverse effects. However, none in the successful group of 13 patients required drug discontinuation because of such effects. Once-a-day oral atenolol as a monotherapy is effective and relatively safe for long-term management of SVT during childhood. It is an attractive alternative β- adrenoceptor blocking agent for the management of pediatric arrhythmias.

We investigated the effects of dietary α-tocopherol and polyunsaturated fatty acids (PUFA) on ischemia-reperfusion injury and cardiac lipid composition. Rats were fed corn oil (CO) diets either deficient (CO - E) or supplemented (CO + E) with RRR-α-tocopherol (100 IU kg-1 diet), or butter oil (BO) diets either deficient (BO - E) or supplemented (BO + E) with RRR-α-tocopherol (100 IU kg-1 diet). Intact rat hearts were subjected to ischemia before reperfusion. Dietary RRR-α-tocopherol supplementation contributed to recovery of aortic output, cardiac output and diastolic pressure after ischemia-reperfusion. In contrast, the type of dietary fat did not influence most measures of cardiac recovery. RRR-α-tocopherol levels in cardiac tissues and plasma were significantly higher for rats fed the BO + E diet than for rats fed the CO + E diet. In contrast to plasma, PUFA in cardiac tissues were maintained at a high level even when rats were fed BO containing diets. Our results suggest that dietary RRR-α-tocopherol, but not dietary PUFA levels, modulate oxidative damage to intact rat hearts during ischemia-reperfusion.

Purpose: To investigate the influence of intensity versus total energy expenditure on neutrophilia and blood oxidative stress to acute exercise. Methods: Nine males (18-30 yr) completed one maximal (Max) and three submaximal exercise sessions: 1) 45 min at 10% above (LT+) lactate threshold (LT), 2) 45 min at 10% below (LT-) LT, and 3) 10% below LT until caloric expenditure equaled the 10%+ trial (LT-kcal). Blood was sampled before (PRE), immediately (POST), 1 h, and 2 h after exercise to measure neutrophils, myeloperoxidase, superoxide (O2-), neutrophil activation (O2-/neutrophils), ascorbic acid, uric acid, malondialdehyde, and lipid hydroperoxides. Results: Intensity-dependent neutrophilia occurred POST exercise with significant increases (P ≤ 0.05) after Max and LT+. A second neutrophilia wave occurred 2 h postexercise. Superoxide was elevated POST (Max) and 2 h post (Max and LT+). In contrast, O2-/neutrophils was increased at 2 h only (Max and LT +). These data indicate that immediately postexercise, total neutrophil number rather than activation best represents neutrophil-generated reactive species within blood. POST Max, ascorbic acid and uric acid were decreased indicating a blood oxidative stress occurred. Alternately, total energy expenditure was not related to any marker of neutrophilia or oxidative stress. Conclusion: Exercise intensity plays a major role in postexercise blood oxidative stress, whereas total exercise energy expenditure does not. Further, neutrophils recruited into circulation during exercise may impose a threshold dependent oxidative stress in blood plasma after exercise.

Prostate cancer is the most common noncutaneous malignancy in men. It is an excellent target for primary prevention. Vitamin E trials conducted for prevention of prostate cancer have had conflicting results with a lower incidence of prostate cancer in the ATBC trial and a higher incidence in the vitamin E arm of the SELECT trial. Most of the clinical trials with vitamin E have been limited to the alpha-tocopherol isoform alone. An increasing body of evidence suggests, however, that the gamma- and delta-isoforms of tocopherol and tocotrienols are more promising with regard to cancer prevention. This review tries to justify our assertion that the gamma- and delta-isoforms of tocopherol and tocotrienol might be superior as prostate cancer preventers.

OBJECTIVES: Veterans of the armed forces, like most population groups, have a high prevalence of vitamin D deficiency, which may be associated with adverse outcomes in several types of cancer. Ultraviolet irradiation is inversely linked with the risk of bladder cancer, presumably through enhanced vitamin D synthesis. We hypothesized that variations in vitamin D status and monitoring predict adverse outcomes in bladder cancer among veterans. METHODS: A retrospective analysis of data in the Veterans Integrated Service Network-9 (southeastern United States) was performed for patients diagnosed between October 1, 1999 and February 29, 2008. Age, tobacco exposure, body mass index, and latitude and seasonality of sampling were included as variables in addition to serum vitamin 25(OH)D levels. RESULTS: Monitoring of vitamin D and vitamin D levels and status were closely linked to survival in bladder cancer. Both the chances of survival and longevity improved with enhanced vitamin D status and monitoring. Veterans with bladder cancer had better outcomes if the initial vitamin D level was higher and had more monitoring of the vitamin. Initial vitamin D levels were more strongly related to outcomes than follow-up levels. The link between vitamin D and outcomes remained after adjusting for background variables such as age, body mass index, latitude, seasonality, and tobacco exposure. CONCLUSIONS: Findings suggest that adequate vitamin D levels early in the course of the disease provide the best opportunity to improve outcomes. Ensuring that veterans with bladder cancer have adequate vitamin D reserves with appropriate monitoring may play a role in improving outcomes in bladder cancer.

Prostate cancer is the most common noncutaneous malignancy in men. It is an excellent target for primary prevention. Vitamin E trials conducted for prevention of prostate cancer have had conflicting results with a lower incidence of prostate cancer in the ATBC trial and a higher incidence in the vitamin E arm of the SELECT trial. Most of the clinical trials with vitamin E have been limited to the alpha-tocopherol isoform alone. An increasing body of evidence suggests, however, that the gamma- and delta-isoforms of tocopherol and tocotrienols are more promising with regard to cancer prevention. This review tries to justify our assertion that the gamma- and delta-isoforms of tocopherol and tocotrienol might be superior as prostate cancer preventers.

OBJECTIVES: Veterans of the armed forces, like most population groups, have a high prevalence of vitamin D deficiency, which may be associated with adverse outcomes in several types of cancer. Ultraviolet irradiation is inversely linked with the risk of bladder cancer, presumably through enhanced vitamin D synthesis. We hypothesized that variations in vitamin D status and monitoring predict adverse outcomes in bladder cancer among veterans. METHODS: A retrospective analysis of data in the Veterans Integrated Service Network-9 (southeastern United States) was performed for patients diagnosed between October 1, 1999 and February 29, 2008. Age, tobacco exposure, body mass index, and latitude and seasonality of sampling were included as variables in addition to serum vitamin 25(OH)D levels. RESULTS: Monitoring of vitamin D and vitamin D levels and status were closely linked to survival in bladder cancer. Both the chances of survival and longevity improved with enhanced vitamin D status and monitoring. Veterans with bladder cancer had better outcomes if the initial vitamin D level was higher and had more monitoring of the vitamin. Initial vitamin D levels were more strongly related to outcomes than follow-up levels. The link between vitamin D and outcomes remained after adjusting for background variables such as age, body mass index, latitude, seasonality, and tobacco exposure. CONCLUSIONS: Findings suggest that adequate vitamin D levels early in the course of the disease provide the best opportunity to improve outcomes. Ensuring that veterans with bladder cancer have adequate vitamin D reserves with appropriate monitoring may play a role in improving outcomes in bladder cancer.

The mevalonate pathway plays an important role in cancer biology and has been targeted with farnesyl transferase inhibitors, although their efficacy is limited due to significant adverse effects. Statins and bisphosphonates inhibit the mevalonate pathway at different steps, thus having negative effects at various levels on cancer cells. A combination of these drugs may result in an amplified cytotoxic effect and allow for use of significantly lower doses of the drugs involved. Statins inhibit the mevalonate pathway at 3-hydroxy-3-methylglutaryl coenzyme A reductase and bisphosphonates at farnesyl pyrophosphate synthase. Our results show that low-dose combinations of simvastatin and alendronate have a synergistic cytotoxic effect on androgen-independent prostate cancer PC-3 cells, but not on androgen-dependent LNCaP or DU 145 prostate cancer cells. These two drugs cause a sequential blockade of the mevalonate pathway and significantly affect survival and apoptotic pathways by down-regulating phospho-AKT and activating c-JUN and ERK.