Dopaminergic gene analysis indicates influence of inattention but not IQ in executive dysfunction of Indian ADHD probands

Abstract

Organizational inefficiency and inattention are speculated to be the reason for executive deficit (ED) of ADHD probands. Even with average IQ, probands often perform poorly due to higher inattention. Pharmacotherapy, cognitive behavioural therapy, and counselling provide only symptomatic relief. Several candidate genes showed involvement with ADHD; the most consistent are dopamine receptor 4 (DRD4) and solute carrier family 6 member 3 (SLC6A3). We analyzed association of rarely investigated DRD4 and SLC6A3 variants with ADHD core traits in Indo-Caucasoid probands. ED, inattention, organizational efficiency, and IQ were measured by Barkley Deficit in Executive Functioning-Child & Adolescent scale, DSM-IV-TR, Conners’ Parent Rating Scale-revised, and WISC respectively. Target sites were analyzed by PCR, RFLP, and/or Sanger sequencing of genomic DNA. DRD4 variants mostly affected inattention while SLC6A3 variants showed association with IQ. Few DRD4 and SLC6A3 variants showed dichotomous association with IQ and inattention. DRD4 Exon3 VNTR >4R showed negative impact on all traits excepting IQ. Inattention showed correlation with attention span, organizational efficiency, and ED, while IQ failed to do so. We infer that IQ and attention could be differentially regulated by dopaminergic gene variants affecting functional efficiency in ADHD and the two traits should be considered together for providing better rehabilitation.     

Accounting for Complexity in Home Telemonitoring: A Need for Context-Centred Evidence

Heart failure represents a significant burden for patients and the Canadian health care system. Home telemonitoring is proposed as an intervention that can improve heart failure outcomes by identifying opportunities for earlier clinical intervention and by providing patients with self-management support between scheduled clinic visits. The objective of this review is to provide clarity with respect to the most recent evidence of the effect of home telemonitoring on heart failure outcomes. Despite some strong evidence that telemonitoring can reduce the risk of mortality and heart failure-related hospitalizations, important inconsistencies exist in the evidence. This article proposes that much of the inconsistency results from differences in the patient population being studied, the type of home telemonitoring intervention, and the implementation setting. Also important is the degree to which intervention fidelity is maintained throughout the course of a study; this is emphasized through a review of the factors that influence the degree to which patients and health care providers use home telemonitoring interventions as intended. In this article we propose that for researchers to produce definitive answers regarding the effect of home telemonitoring on heart failure outcomes, interventions and studies need to be designed and tailored according to the characteristics of the target patient population and the implementation context.     

Brachydactyly type E in an Italian family with 6p25 trisomy

Brachydactyly type E is a congenital limb malformation characterized by small hands and feet as a result of shortened metacarpals and metatarsals. Genetic causes of this anomaly are heterogeneous and only partially characterized. In this report we describe an Italian family in which four subjects share brachydactyly type E and a 3 Mb microduplication in region 6p25. The duplication involves the gene FOXC1, expressed during the osteoblast differentiation, which appears a potential candidate gene for brachydactyly.     

Ex vivo all-trans retinoic acid modulates NO production and regulates IL-6 effect during rheumatoid arthritis: a study in Algerian patients

Rheumatoid arthritis (RA) is a chronic autoimmune disease. The pathophysiology of RA implicates several mediators such as nitric oxide (NO) and cytokines such as interleukin-6 (IL-6), which is deeply involved in the main characteristics of RA. Furthermore, all-trans retinoic acid (ATRA) is an active vitamin A derivative well-known to have diverse immunomodulatory actions. In our study, we investigated first, the ex vivo immunomodulatory potential of ATRA on NO pathway by peripheral blood mononuclear cells (PBMCs) from Algerian RA patients. Then, we assessed the possible regulatory effect of ATRA on NO production induced by IL-6. PBMCs isolated from active and inactive RA patients and healthy controls were cultured with different concentrations of IL-6 or/with ATRA. NO production was assessed using the Griess method. Inducible nitric oxide synthase expression and NF-κB activity were analyzed by immunofluorescence test. Our results revealed a high NO production during active RA. We noticed that while IL-6 induced a high NO production and iNOS expression, ATRA downregulated both. ATRA also inhibited nuclear NF-κB translocation. Interestingly, it seems that NO production mediated by IL-6 on PBMCs of RA patients is downregulated by ATRA. Taken together, our results highlight the immunomodulatory effect of ATRA on NO pathway in RA patients and its possible role in regulating IL-6-mediated NO production. All these findings suggest its potential therapeutic role during RA.     

Anthelmintic activity of cyclotides: In vitro studies with canine and human hookworms

Hookworm infection is a leading cause of maternal and child morbidity in countries of the tropics and subtropics, as well as being an important parasite in companion-animal medicine. The cyclotides are a novel family of cyclic cystine knot containing peptides from plants that have been shown to possess anthelmintic activity against Haemonchus contortus and Trichostrongylus colubriformis, two important gastrointestinal nematodes of sheep. In the current study we demonstrated the in vitro effects of three representative cyclotides, kalata B1, kalata B6 and cycloviolacin O14, on the viability of larval and adult life stages of the dog hookworm Ancylostoma caninum, and larvae of the human hookworm Necator americanus. The cyclotides showed significant anthelmintic activity towards both hookworm species. The different cyclotides showed similar patterns of relative activity as that seen previously with the livestock nematode species. This study demonstrates that cyclotides have promising activity in vitro against important parasites of companion animals and humans.