An Exploration of Sleep and Family Factors in Young Children at Familial Risk for ADHD.

Objective: The aim of the current study was to examine relations between sleep problems and family factors and early markers of ADHD in young children with and without a familial risk for ADHD.Methods: Differences in sleep behavior and family functioning in children under 6 years with (n = 72) and without (n = 139) a familial risk for ADHD were investigated. The influence of family and sleep factors on the development of early temperament markers of ADHD (effortful control and negative affect) was explored. Parents/caregivers completed questionnaires on family functioning, child sleep behavior, and general regulatory behaviors.Results: A significant difference was observed between high-risk and low-risk groups for family functioning in the infant/toddler (<3 years) and preschool (>3 years) cohorts. Parents of infants/toddlers in the high-risk group reported poorer infant sleep. However, there were no sleep differences reported for the preschool cohort. Family functioning was found to predict effortful control, while sleep quality predicted negative affect.Conclusion: The results of this study highlight potential family and sleep issues for young children with a familial history of ADHD and the potential influence of these factors on early temperament markers of ADHD. Future research should explore these relations further in order to better establish whether early sleep and family interventions could mitigate later ADHD symptomatology.

Cistromic and genetic evidence that the vitamin D receptor mediates susceptibility to latitude-dependent autoimmune diseases.

The vitamin D receptor (VDR) is a ligand-activated transcription factor that regulates gene expression in many cell types, including immune cells. It requires binding of 1,25 dihydroxy vitamin D3 (1,25D3) for activation. Many autoimmune diseases show latitude-dependent prevalence and/or association with vitamin D deficiency, and vitamin D supplementation is commonly used in their clinical management. 1,25D3 is regulated by genes associated with the risk of autoimmune diseases and predominantly expressed in myeloid cells. We determined the VDR cistrome in monocytes and monocyte-derived inflammatory (DC1) and tolerogenic dendritic cells (DC2). VDR motifs were highly overrepresented in ChIP-Seq peaks in stimulated monocyte (40%), DC1 (21%) and DC2 (47%), P

Brachytherapy for high grade prostate cancer induces distinct changes in circulating CD4 and CD8 T cells - Implications for systemic control.

This exploratory study is a follow up to our previous investigation of immune response in the circulation of high-grade Gleason 9 prostate cancer patients treated with EBRT + BT compared to EBRT alone. Notably, EBRT + BT demonstrates the potential to elicit an effect on CD4/CD8 ratio which may have attributed to improved clinical response to therapy. Our findings show promise for leveraging circulating immune cells as predictive biomarkers for radiotherapy response.

Secular trends in nosocomial bloodstream infections: antibiotic-resistant bacteria increase the total burden of infection.

BACKGROUND: It is unknown whether rising incidence rates of nosocomial bloodstream infections (BSIs) caused by antibiotic-resistant bacteria (ARB) replace antibiotic-susceptible bacteria (ASB), leaving the total BSI rate unaffected. METHODS: We investigated temporal trends in annual incidence densities (events per 100 000 patient-days) of nosocomial BSIs caused by methicillin-resistant Staphylococcus aureus (MRSA), ARB other than MRSA, and ASB in 7 ARB-endemic and 7 ARB-nonendemic hospitals between 1998 and 2007. RESULTS: 33 130 nosocomial BSIs (14% caused by ARB) yielded 36 679 microorganisms. From 1998 to 2007, the MRSA incidence density increased from 0.2 to 0.7 (annual increase, 22%) in ARB-nonendemic hospitals, and from 3.1 to 11.7 (annual increase, 10%) in ARB-endemic hospitals (P = .2), increasing the incidence density difference between ARB-endemic and ARB-nonendemic hospitals from 2.9 to 11.0. The non-MRSA ARB incidence density increased from 2.8 to 4.1 (annual increase, 5%) in ARB-nonendemic hospitals, and from 1.5 to 17.4 (annual increase, 22%) in ARB-endemic hospitals (P < .001), changing the incidence density difference from -1.3 to 13.3. Trends in ASB incidence densities were similar in both groups (P = .7). With annual increases of 3.8% and 5.4% of all nosocomial BSIs in ARB-nonendemic and ARB-endemic hospitals, respectively (P < .001), the overall incidence density difference of 3.8 increased to 24.4. CONCLUSIONS: Increased nosocomial BSI rates due to ARB occur in addition to infections caused by ASB, increasing the total burden of disease. Hospitals with high ARB infection rates in 2005 had an excess burden of BSI of 20.6 per 100 000 patient-days in a 10-year period, mainly caused by infections with ARB.

Executive function in children with sickle cell anemia on transfusion: NIH toolbox utility in the clinical context.

Objective: The aim of this study was to establish the utility of the NIH Toolbox as a cognitive screener of executive functions in the clinical context. Additionally, we aimed to investigate whether age and time on transfusion were related to executive function performance. Method: Twenty-eight children and adolescents with sickle cell anemia (SCA) between 8 and 18 years (M = 13.28, SD = 3.05) on transfusion treatment were included. Participants completed five NIH Toolbox tasks (three executive function tasks and two non-executive function control tasks). Results: Mean scores on one of the three executive function measures (inhibitory control) fell below the average range (M = 81.36, SD = 14.01) with approximately 70% of children from both groups below the average range. Scores for processing speed (M = 86.82, SD = 22.01) and cognitive flexibility (M = 85.75, SD = 12.67) were low averages. As expected, scores on non-executive measures (language and memory) fell within the average range. No significant differences were observed between children with silent stroke and no stroke on executive function measures. Older age (p < .01) and length of time on transfusion (p < .05) predicted lower inhibitory control scores. Conclusions: Findings provide evidence for poor development of inhibitory control with age in this patient population. As the NIH Toolbox successfully highlighted expected deficits in this patient population, this study supports the use of this tool as a brief screening measure for children with SCD. The clinical and theoretical implications of the findings are discussed.

Analysis of trends and seasonal variation in primary cutaneous melanoma: an Irish study.

A seasonal variation in the presentation of cutaneous melanoma has been documented in several studies. We performed a retrospective review of primary cutaneous melanomas (n = 263) from our institution to examine whether the seasonal patterns of presentation noted in the literature would be similar in Ireland, a climate with low ambient sunshine. A summer : winter ratio was determined for age, gender, subtype, location and Breslow thickness. We found an increase in total numbers of melanomas, particularly in men. The summer : winter ratio was 2.39 for all patients (95% CI 1.60-3.57, P < 0.001), with seasonal variations noted for location, thickness and subtype (excluding lentigo). Melanomas presenting over the summer tended towards a greater Breslow thickness than did those presenting in winter. This subclassification of primary cutaneous melanoma with summer : winter ratios based on patient and tumour characteristics gave remarkably similar results to previously published reports, notwithstanding the low levels of annual ambient sunshine in Ireland.

Cutaneous reactions to adalimumab administration.

Patients receiving antitumour necrosis factor-alpha treatment may develop cutaneous reactions. This human monoclonal antibody is used in the treatment of chronic inflammatory diseases, including arthritis and inflammatory bowel disease. A variety of side effects have been documented ranging from infection and vasculitis through to systemic lupus erythematosus and psoriasis. We report on two arthritic patients treated with adalimumab (Humira, Abbot Laboratories, IL, USA) who developed new onset rashes that resolved with discontinuation of therapy. The frequency of these cutaneous reactions has not been fully established and may benefit from a centralised registry.

Sensory modulation and negative affect in children at familial risk of ADHD.

BACKGROUND/AIMS: Sensory modulation difficulties are commonly reported in patients with ADHD, however there has been little focus on the development of these difficulties in young children at a higher risk of later ADHD diagnosis. This study investigated whether children with a familial history of ADHD show greater sensory modulation difficulties. We also explored whether sensory modulation was linked to negative affectivity, which has been highlighted as a potential early marker of ADHD. METHODS: Parents of children under 6 years with a family history of ADHD (n = 65) and no family history (n = 122) completed questionnaires on sensory modulation and temperament. RESULTS: Children from families with ADHD were reported to display extreme patterns of hyperresponsiveness and hyporesponsiveness, relative to controls. No differences emerged for the sensory seeking domain. Some children within the high-risk group reported high scores across all three sensory modulation patterns. Regression analysis revealed that hyperresponsiveness predicted higher levels of negative affect. CONCLUSIONS/IMPLICATIONS: This study is the first to report greater sensory modulation difficulties in children at familial risk of ADHD. Future research should establish whether children with sensory modulation and temperament difficulties in early childhood are more vulnerable to developing ADHD.

Immune cell profiling in Gleason 9 prostate cancer patients treated with brachytherapy versus external beam radiotherapy: An exploratory study.

This exploratory study evaluates immunological changes in high-risk Gleason 9 prostate cancer patients treated with EBRT+BT compared to EBRT alone. Notably, BT demonstrates the potential to elicit a T cell response which may support further investigation using circulating immune cells as predictive and prognostic biomarkers for radiotherapy response.

Detecting soluble clusterin in in-vitro and in-vivo models of prostate cancer.

PSA, the only relevant marker for prostate cancer, has a low predictive value; moreover its low threshold leads to unnecessary biopsies with associated complications. Identification of prognostic factors is an important goal in prostate cancer. In the search for new markers, clusterin, has some potential as it is closely linked with cancer progression and resistance to apoptosis. We looked at the expression of secreted clusterin (sCLU) in prostate cells to determine correlations with progression and drug resistance. The plasmatic expression of sCLU was also investigated in order to use it as a potential marker for prostate cancer. sCLU expression was studied using Western blotting on cultured prostate cells, PWR-1E, PC3 and PC3 Docetaxel resistant cells in the cytosol and culture medium. An inhouse ELISA test was developed to determine sCLU expression in culture media and plasma samples. A patient cohort was identified from the Prostate Cancer Research Consortium Bio-Resource and plasmatic expression of sCLU was studied using western blotting and the inhouse ELISA test. Only the fully processed form of sCLU was identified in the medium of cells with increased expression associated with increased progression of disease and resistance to docetaxel. Plasmatic expression of sCLU was significantly higher in the plasma of patients with high grade prostate cancer with extracapsular extension than in the plasma of prostate cancer patients without extracapsular extension. Plasmatic sCLU may be an effective prognostic marker of prostate cancer and needs to be tested in a multimarker approach.