Synthesis, characterization, and anti-melanoma activity of tetra-O-substituted analogs of nordihydroguaiaretic acid.

Synthesis of seven semi-synthetic analogs of NDGA is described. An approach to NDGA derivatization is described in which the ortho-phenolic groups are tethered together by one atom, forming a 5-membered heterocyclic ring. The analogs were evaluated for cytotoxicity in four cancer cell lines and compared to NDGA and tetra-O-methyl-NDGA (M4N) (1a).

Predictive power of pretreatment prognostic factors in children with hepatoblastoma: a report from the Children's Oncology Group.

Background: PRETEXT is used to stratify risk in children with hepatoblastoma by the Liver Tumor Strategy Group (SIOPEL) of the International Society of Pediatric Oncology (SIOP). A recent analysis excluding patients that did not survive neoadjuvant chemotherapy, concluded that PRETEXT was superior to Children's Oncology Group (COG) stage for predicting survival. Puzzled by this result, we made a similar comparison of PRETEXT and COG stage.

RNA interference-mediated silencing of the respiratory syncytial virus nucleocapsid defines a potent antiviral strategy.

We describe the design and characterization of a potent human respiratory syncytial virus (RSV) nucleocapsid gene-specific small interfering RNA (siRNA), ALN-RSV01. In in vitro RSV plaque assays, ALN-RSV01 showed a 50% inhibitory concentration of 0.7 nM.

Pretreatment with nitroprusside for microcirculatory protection in saphenous vein graft interventions.

Objectives: We hypothesized that the prophylactic administration of sodium nitroprusside (NTP) during saphenous vein graft (SVG) PCI would ameliorate the detrimental effects of distal embolization and reduce the frequency and magnitude of post-procedural myonecrosis.

Methods: Sixty-four consecutive patients with normal preprocedural cardiac enzymes underwent SVG PCI without embolic protection devices and received prophylactic intragraft NTP before initial device activation. For each case, 2 control patients were selected in reverse chronologic order and were matched for stent use, thromboatherectomy device use, clinical presentation, presence of thrombus and pre-PCI thrombolysis in myocardial infarction (TIMI) flow.

Division of the fistula in laparoscopic-assisted repair of anorectal malformations-are clips or ties necessary?

Background: Laparoscopic-assisted anorectoplasty (LAARP) was introduced in 2000 by Georgeson (J Pediatr Surg. 2000;35:927-930) and has gained interest because of improved visualization of the rectal fistula and the ability to place the pull-through segment within the levator muscle complex with minimal dissection. Currently, there is no consensus on how the fistula should be managed during LAARP.

Outpatient nutrition management of the neurologically impaired child.

The nutrition care of children who are neurologically impaired is a challenge for the nutrition care team. Many factors should be considered in the assessment and development of a nutrition plan. That these children can have significant abnormalities in nutrition status, growth, and body composition should be kept in mind.

5'-Triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma.

Genetic and epigenetic plasticity allows tumors to evade single-targeted treatments. Here we direct Bcl2-specific short interfering RNA (siRNA) with 5'-triphosphate ends (3p-siRNA) against melanoma. Recognition of 5'-triphosphate by the cytosolic antiviral helicase retinoic acid-induced protein I (Rig-I, encoded by Ddx58) activated innate immune cells such as dendritic cells and directly induced expression of interferons (IFNs) and apoptosis in tumor cells.

Routine use of a SILASTIC spring-loaded silo for infants with gastroschisis: a multicenter randomized controlled trial.

Background: Retrospective studies have suggested that routine use of a preformed silo for infants with gastroschisis may be associated with improved outcomes. We performed a prospective multicenter randomized controlled trial to test this hypothesis.

Methods: Eligible infants were randomized to (1) routine bedside placement of a preformed Silastic spring-loaded silo, with gradual reduction and elective abdominal wall closure, or (2) primary closure.

Development and psychometric evaluation of the pleasant activities list.

This paper describes the development of a new 139-item behavioral questionnaire (PAL) assessing the frequency and enjoyability of pleasant activities occurring in the natural environment of patients with substance use disorders. The sample consisted of 265 patients with mainly substance use disorders and 272 healthy controls. Group comparisons indicated that patients reported lower frequency, enjoyability, and cross-product activity scores than controls.

Mental health (GHQ12; CES-D) and attitudes towards the value of work among inmates of a semi-open prison and the long-term unemployed in Luxembourg.

Aim: To analyse the relationships between mental health and employment commitment among prisoners and the long-term unemployed (LTU) trying to return to work.

Method: Fifty-two of 62 male inmates of a semi-open prison (Givenich Penitentiary Centre, the only such unit in Luxembourg), and 69 LTU registered at the Luxembourg Employment Administration completed a questionnaire exploring: 1) mental health (measured by means of scales GHQ12 and CES-D); 2) employment commitment; 3) availability of a support network, self-esteem, empowerment; and 4) socio-demographic characteristics.

Results: Compared with LTU, inmates were younger, more had work experience (54.

Closed gastroschisis: total parenteral nutrition-free survival with aggressive attempts at bowel preservation and intestinal adaptation.

Background: In infants with gastroschisis antenatal closure of the umbilical defect results in a proximal atresia with ischemia and/or volvulus of the extracorporeal midgut. It has been described as "closed gastroschisis" or "vanishing midgut."

Methods: A 10-year review of 219 gastroschisis patients identified 10 infants with this rare complication.

Anatomy and histochemistry of hindlimb flight posture in birds. I. The extended hindlimb posture of shorebirds.

Birds utilize one of two hindlimb postures during flight: an extended posture (with the hip and knee joints flexed, while the ankle joint is extended caudally) or a flexed posture (with the hip, knee, and ankle joints flexed beneath the body). American Avocets (Recurvirostra americana) and Black-necked Stilts (Himantopus mexicanus) extend their legs caudally during flight and support them for extended periods. Slow tonic and slow twitch muscle fibers are typically found in muscles functioning in postural support due to the fatigue resistance of these fibers.

Evaluation of the safety, tolerability and pharmacokinetics of ALN-RSV01, a novel RNAi antiviral therapeutic directed against respiratory syncytial virus (RSV).

Small interfering RNAs (siRNAs) work through RNA interference (RNAi), the natural RNA inhibitory pathway, to down-regulate protein production by inhibiting targeted mRNA in a sequence-specific manner. ALN-RSV01 is an siRNA directed against the mRNA encoding the N-protein of respiratory syncytial virus (RSV) that exhibits specific in vitro and in vivo anti-RSV activity. The results of two safety and tolerability studies with ALN-RSV01 involving 101 healthy adults (65 active, 36 placebo, single- and multiple dose, observer-blind, randomized dose-escalation) are described.

Surgical resection of pulmonary metastatic lesions in children with hepatoblastoma.

Background: Although the most common site of metastasis for hepatoblastoma is the lung, the role of thoracotomy and surgical resection of pulmonary metastasis remains uncertain. In this study, we aimed to determine the long-term outcome of patients with hepatoblastoma who have a surgical resection of pulmonary metastatic lesions.

Methods: Patients with hepatoblastoma in the Children's Oncology Group INT-0098 were reviewed.

Improvement of in vitro thrombolysis employing magnetically-guided microspheres.

Significant shortcomings in clinical thrombolysis efficiencies and arterial recanalization rates still exist to date necessitating the development of additional thrombolysis-enhancing technologies. For example, to improve tPA-induced systemic clot lysis several supplementary treatment methods have been proposed, among them ultrasound-enhanced tissue plasminogen activator (tPA) thrombolysis which has already found some clinical applicability. The rationale of this study was to investigate whether biodegradable, magnetic spheres can be a useful adjuvant to currently existing tPA-induced thrombolysis and further enhance clot lysis results.

Variability in glycosylated hemoglobin values in diabetic patients living in long-term care facilities.

Objectives: The objectives of this study were to determine the prevalence of diabetes and mean A1C of patients in long-term care facilities (LTCFs); to determine differences in A1C values based on patient characteristics; and to examine the self-reported practices of providers regarding diabetes management goals.

Design: Twelve-month retrospective review of patient charts; survey of physicians and nurse practitioners providing care to these patients.

Setting: Nursing facility practice of an urban teaching hospital.

Tumors of the liver in children.

In this review we examine the diagnosis and treatment of pediatric liver tumors- both malignant and benign. The two most common malignant tumors are hepatoblastoma and hepatocellular carcinoma. Hepatoblastoma is seen in younger children, hepatocellular carcinoma in older children.

Temporary abdominal vacuum-packing closure in the neonatal intensive care unit.

Background: Temporary abdominal vacuum-packing (vac-pac) closure is well known in adult literature, yet has not been reported in infants.

Methods: A review of children in the neonatal intensive care unit who underwent vac-pac closure from 2000 to 2006 was performed.

Results: During this time, 7 infants underwent vac-pac closure after abdominal surgery.

Preclinical antitumor activity, pharmacokinetics and pharmacodynamics of imexon in mice.

Imexon, a novel pro-oxidant, thiol-binding agent, is currently in phase I/II clinical trials in patients with advanced solid tumors. The aim of this study was to characterize the preclinical pharmacology of imexon in vivo. We investigated the anticancer activity of imexon in several cancer cell lines grown as xenografts in severe combined immunodeficient mice.

Cytotoxic activity of Apomine is due to a novel membrane-mediated cytolytic mechanism independent of apoptosis in the A375 human melanoma cell line.

Apomine, a novel bisphosphonate ester, has demonstrated anticancer activity in a variety of cancer cell lines; however, its mechanism of cytotoxicity is not well understood. Previous work has demonstrated that Apomine induces cell death by activation of caspase-3 in several cancer cell types. However, we have demonstrated that Apomine induces cell death in the A375 human melanoma cell line through a novel membrane-mediated mechanism that is independent of caspase-3 activation.

Treatment outcome for street-living, homeless youth.

Comprehensive intervention for homeless, street living youth that addresses substance use, social stability, physical and mental health issues has received very little attention. In this study, street living youth aged 14-22 were recruited from a drop-in center and randomly assigned to the Community Reinforcement Approach (CRA) or treatment as usual (TAU) through a drop-in center. Findings showed that youth assigned to CRA, compared to TAU, reported significantly reduced substance use (37% vs.

Horse soleus muscle: postural sensor or vestigial structure?

The soleus muscle of horses is rather diminutive with respect to the overall size of adjacent synergist muscles in the hind limb of the horse. Whether or not such a muscle might be vestigial or may be providing some essential function has not been determined. We have studied the horse's soleus muscle using histochemical (ATPase), immunocytochemical (myosin isoform identification), and SDS-PAGE analysis to demonstrate that it is largely composed of 100% type I, presumed slow-twitch fibers.

Dorsal hippocampus inhibition disrupts acquisition and expression, but not consolidation, of cocaine conditioned place preference.

Cocaine abusers may experience drug craving upon exposure to environmental contexts where cocaine was experienced. The dorsal hippocampus (DHC) is important for contextual conditioning, therefore the authors examined the specific role of the DHC in cocaine conditioned place preference (CPP). Muscimol was used to temporarily inhibit the DHC and was infused before conditioning sessions or tests for CPP to investigate acquisition and expression of cocaine CPP, respectively.