Characterizing Goal-Directed Behavior in Children with Attention-Deficit/Hyperactivity Disorde

Attention-deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention, impulsivity and hyperactivity. Children with ADHD show impaired motivational behavior. For example, they tend to select small, immediate over large, delayed rewards. They might be unable to predict the consequences of their actions showing a deficit in action-control strategies. Goals and habits are the two behavioral mechanisms that control actions. Balancing these two behaviors leads to normal action-control. In previous studies, we found that rat models of ADHD demonstrated over-reliance on habits and poor goal-directed actions. This deficit was restored by administering methylphenidate (the most commonly used psychostimulant in ADHD treatment), dopamine D2 receptor agonist or dopamine D1 receptor antagonist. Further, in another pilot study, we found that children with ADHD are less reliant on goal-directed behavior compared to healthy children. In this study, we examined action-control patterns in children with ADHD on- and off- methylphenidate. We hypothesize that on-methylphenidate patients will show different patterns of action-control compared to off-methylphenidate patients. We tested 7 off-medication and 7 on-medication, 6-10 years old children with ADHD, and 13 healthy controls. Participants were 6-10 years old and were group matched for age and sex. We tested patterns of action-control using a computer-based task of the outcome devaluation paradigm that consists of three phases; a training phase, a devaluation phase and a choice test. Children with ADHD were successful at acquiring action-outcome associations as well as showing higher tendency on goal-directed responses. However, throughout the task, on- methylphenidate children showed (1) lower number of errors, (2) higher reaction times and (3) no difference in action-control responses (goals vs. habits). These results indicate that methylphenidate was beneficial in modulating symptoms of ADHD by reducing the number of errors during learning and increasing children’s response times; but it was not effective in improving children’s cognitive profile, reflected by similar action-control patterns in both on and off-medication states

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

[Insignificant prostate cancer: charateristics and predictive factors].

The widespread screening for PSA has contributed to the increased incidence of prostate cancer (PCa), mostly identifying disease at earlier stages. Many of these patients will probably not require treatment because of the indolent course of the disease. The European Randomized Study of Screening for Prostate Cancer (ERSPC) has showed that 1410 men needed to be screened and 48 prostatectomies performed to prevent death. The aim of this study was to evaluate predictive factors of insignificant PCa in our experience.We analyzed various preoperative clinical and biopsy findings of 225 consecutive patients who underwent prostatectomy from October 2007 to June 2010. The indication for biopsy was placed in presence of an abnormal rectal examination and/or suspected transrectal ultrasound and/or PSA >4 ng/ml. We consider insignificant a tumor with a volume ≤5\% of the entire gland with a Gleason score ≤ 6, with no grades 4 or 5 and organ confined.The prevalence of potentially insignificant PCa in our experience was 12\%. The preoperative findings of patients with insignificant PCa were significantly more favorable than the remaining cases with PCa not insignificant. Multivariate analysis did not reveal any independent predictors.In our experience, in a population not screened for PCa, we have not identified any factors that can predict with certainty the insignificant nature of a tumor and, therefore, useful to start a patient on an active surveillance program

Pancreatic cancer-associated diabetes is correlated with increased liver nitric oxide (NO)

Background: In pancreatic cancer-associated diabetes mellitus (PC-DM) an altered liver and muscle glucose metabolism occurs. NO modifies glucose release by isolated hepatocytes. Our aims were to verify whether PC-DM determines in the liver: 1. an increased NO production, 2. an altered action and/or mRNA levels of the glycolytic enzyme GAPDH, which catalyzes a critical reaction in gluconeogenesis and which could be inhibited by NO. Patients and Methods: 23 patients with pancreatic cancer (PC, n 17) or chronic pancreatitis (CP; n 6) were studied. In liver tissue homogenates the following were assayed: GAPDH mRNA (quantitative RT-PCR, BioSource, USA), l-glucose, l-lactate, l-urea, l-nitrite and l-nitrate (Roche, Italy)(indirect indices of NO production), and l-GAPDH activity. Results: DM was diagnosed in 12 PC and 3 CP. No significant association was observed between DM and disease diagnosis (X2 1.75, p:ns). None of the parameters evaluated varied in relation to the presence of PC or CP. Considering patients with PC only, higher mean levels of GAPDH mRNA (t 2.15, p 0.05), l-nitrite (t 2.30, p 0.05), l-lactate (t 2.2, p 0.05), l-urea (t 2.38, p 0.05) and l-glucose (t 2.00, p 0.064) were found in patients with than in those without DM. In PC the variations of GAPDH mRNA copies were correlated with the serum levels of fasting glucose (r 0.78, p 0.001) and with l-GAPDH activity (r 0.508, p 0.05); l-nitrite levels correlated with l-glucose (r 0.594, p 0.05), l-lactate (r 0.654, p 0.01) and l-urea (r 0.758, p 0.01) levels. The variations of l-glucose were correlated with those of l-lactate (r 0.913, p 0.001) and of l-urea (r 0.559, p 0.05). Conclusion: In the liver of patients with PC-DM, NO synthesis is induced; this increased production does not inhibit, as expected, GAPDH activity nor urea production. The increased levels of liver GAPDH mRNA copies in PC-DM might be a physiological response to hyperglycemia, while the increased urea content in the same patients might be a consequence of an enhanced proteolysis which parallels glucose metabolic alterations